Delivery of radiation by column and generating a treatment plan therefor

ABSTRACT

An example method of treating a target using particle beam includes directing the particle beam along a path at least part-way through the target, and controlling an energy of the particle beam while the particle beam is directed along the path so that the particle beam treats at least interior portions of the target that are located along the path. While the particle beam is directed along the path, the particle beam delivers a dose of radiation to the target that exceeds one (1) Gray-per-second for a duration of less than five (5) seconds. A treatment plan may be generated to perform the method.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a continuation of U.S. patent application Ser. No.16/811,130, which was filed on Mar. 6, 2020, and which is titled“Delivery Of Radiation By Column and Treatment Plan Therefor. U.S.patent application Ser. No. 16/811,130 is incorporated herein byreference. U.S. patent application Ser. No. 16/811,130 and, thereforethis application, claims priority to, and the benefit of, U.S.Provisional Patent Application No. 62/815,721, which was filed Mar. 8,2019, and which is titled “Delivery Of Radiation By Column”. U.S. patentapplication Ser. No. 16/811,130 and, therefore this application, claimspriority to, and the benefit, of U.S. Provisional Patent Application No.62/853,387, which was filed on May 28, 2019, and which is titled “EnergyDegrader Including Boron Carbide”. U.S. patent application Ser. No.16/811,130 and, therefore this application, claims priority to, and thebenefit, of U.S. Provisional Patent Application No. 62/889,825, whichwas filed on Aug. 21, 2019, and which is titled “Generating A TreatmentPlan”. U.S. patent application Ser. No. 16/811,130 and, therefore thisapplication, claims priority to, and the benefit, of U.S. ProvisionalPatent Application No. 62/889,861, which was filed on Aug. 21, 2019, andwhich is titled “Collimator For A Particle Therapy System”. The contentsof U.S. Provisional Patent Applications Nos. 62/815,721, 62/853,387,62/889,825, and 62/889,861 are incorporated herein by reference.

TECHNICAL FIELD

This disclosure relates generally to a particle therapy system thatdelivers doses of radiation by column and to generating a treatment plantherefor.

BACKGROUND

Particle therapy systems use an accelerator to generate a particle beamfor treating afflictions, such as tumors. In operation, particles areaccelerated in orbits inside a cavity in the presence of a magneticfield and are removed from the cavity through an extraction channel. Amagnetic field regenerator generates a magnetic field bump near theoutside of the cavity to distort the pitch and angle of some orbits sothat they move towards, and eventually into, the extraction channel. Abeam, comprised of the particles, exits the extraction channel.

A scanning system is down-beam of the extraction channel. In thisexample, down-beam suggests closer to an irradiation target relative tothe extraction channel. The scanning system moves the particle beamrelative to the irradiation target to expose various parts of theirradiation target to the particle beam. For example, to treat a tumor,the particle beam may be scanned over different parts of the tumor toexpose the different parts to radiation.

Particle therapy systems typically operate in accordance with atreatment plan. A treatment plan may specify, among other things, dosesof radiation to be delivered to the patient by the particle therapysystem.

SUMMARY

An example method of treating a target using a particle beam includesdirecting the particle beam along a path at least part-way through thetarget, and controlling an energy of the particle beam while theparticle beam is directed along the path so that the particle beamtreats at least interior portions of the target that are located alongthe path. While the particle beam is directed along the path, theparticle beam delivers a dose of radiation to the target that exceedsone (1) Gray-per-second for a duration of less than five (5) seconds.The example method may include one or more of the following features,either alone or in combination.

Directing and controlling may be performed for each of multiplemicro-volumes of the target. Controlling the energy of the particle beammay include moving one or more energy-absorbing plates into or out ofthe path of the particle beam between the target and a source of theparticle beam. Moving the one or more energy-absorbing plates into orout of the path of the particle beam may be performed while the particlebeam is directed along the path. Moving the one or more energy-absorbingplates into or out of the path of the particle beam may include movingmultiple energy-absorbing plates sequentially into the path of theparticle beam. Moving the one or more energy-absorbing plates into orout of the path of the particle beam may include moving multipleenergy-absorbing plates sequentially out of the path of the particlebeam. An energy-absorbing plate among the one or more energy-absorbingplates may include a linear motor that is controllable to move theenergy-absorbing plate into or out of the path of the particle beam.Each of the one or more energy-absorbing plates may be movable into orout of the path of the particle beam in a duration of one hundred (100)milliseconds or less. Each of the one or more energy-absorbing platesmay be movable into or out of the path of the particle beam in aduration of fifty (50) milliseconds or less. Each of the one or moreenergy-absorbing plates may be movable into or out of the path of theparticle beam in a duration of ten (10) milliseconds or less. Moving theone or more energy-absorbing plates into or out of the path of theparticle beam may include controlling a first plate among the one ormore energy-absorbing plates to move during passage of the particle beamthrough the one or more energy-absorbing plates to the target. The firstplate being may be configured and controllable to move across at leastpart a beam field. The beam field may correspond to a plane defining amaximum extent that the particle beam can move relative to the target.

The particle beam may be produced by a particle accelerator configuredto output a particle beam that is based on a current throughsuperconducting windings contained within the particle accelerator.Controlling the energy of the particle beam may include setting thecurrent to one of multiple values. Each of the multiple values maycorrespond to a different energy at which the particle beam is outputfrom the particle accelerator. While the particle beam is directed alongthe path, the particle beam may deliver a dose of radiation to thetarget that exceeds twenty (20) Gray-per-second for a duration of lessthan five seconds. While the particle beam is directed along the path,the particle beam may deliver a dose of radiation to the target that isbetween twenty (20) Gray-per-second and one hundred (100)Gray-per-second for a duration of less than five seconds. While theparticle beam is directed along the path, the particle beam may delivera dose of radiation to the target that is between forth (40)Gray-per-second and one hundred and twenty (120) Gray-per-second. The 40to 120 Gray-per-second dose may be for less than five seconds. While theparticle beam is directed along the path, the particle beam may delivera dose of radiation to the target that that exceed one or more of thefollowing doses for a duration of less than 500 ms, for a duration thatis between 10 ms and 5 s, or for a duration that is less than 5 s: 100Gray-per-second, 200 Gray-per-second, 300 Gray-per-second, 400Gray-per-second, or 500 Gray-per-second. The particle beam may be aGaussian pencil beam having a size of at least two (2) millimeterssigma. The particle beam may be a Gaussian pencil beam having a sizebetween two (2) millimeters sigma and twenty (20) millimeters sigma.

The path may be a first path and the method may include directing theparticle beam along a second path at least part-way through the targetthat is different from the first path. The method may includecontrolling the energy of the particle beam while the particle beam isdirected along the second path so that the particle beam treats portionsof the target that are located along the second path. For example, thefirst and second paths may be columns that extend through the target allthe way or part of the way. While the particle beam is directed alongthe second path, the particle beam may deliver a dose of radiation tothe target that exceeds one (1) Gray-per-second for a duration of lessthan five hundred (500) milliseconds. The particle beam may never againbe directed along the first path during treatment of the target in someexamples.

The method may include blocking at least part of the particle beam usinga collimator that is configurable to block a first part of the particlebeam while allowing a second part of the particle beam to reach thetarget. The collimator may include structures comprised of material thatblocks passage of the particle beam. The structures may define an edgethat moves into the path of the particle beam such that the first partof the particle beam on a first side of the edge is blocked by thestructures and such that the second part of the particle beam on asecond side of the edge is not blocked by the structures. The collimatormay include linear motors that are controlled to configure thestructures to define the edge. Each of the linear motors may include amovable component and a stationary component. The stationary componentmay include a magnetic field generator to generate a first magneticfield. The movable component may include one or more coils to conductcurrent to produce a second magnetic field that interacts with the firstmagnetic field to cause the moveable component to move relative to thestationary component. The movable component of each linear motor may beconnected to, or may be part of, a corresponding one of the structuressuch that the corresponding structure moves along with movement with themovable component.

An example method of treating a target using a particle beam includesdirecting the particle beam along a first path at least part-way throughthe target, controlling an energy of the particle beam while theparticle beam is directed along the first path so that the particle beamtreats a three-dimensional columnar portion of the target that is alongthe first path, and repeating directing the particle beam andcontrolling the energy for multiple different paths at least part-waythrough the target without directing the beam along a same path throughthe target more than once. While the particle beam is directed alongeach path through the target, the particle beam may deliver a dose ofradiation to the target that exceeds one (1) Gray-per-second for aduration of less than five (5) seconds. The example method may includeone or more of the following features, either alone or in combination.

Directing and controlling may be performed for each of multiplemicro-volumes of the target. Controlling the energy of the particle beammay include moving one or more energy-absorbing plates into or out of apath of the particle beam between the target and a source of theparticle beam. The particle beam may be produced by a particleaccelerator configured to output a particle beam that is based on acurrent through superconducting windings contained within the particleaccelerator. Controlling the energy of the particle beam may includesetting the current to one of multiple values. Each of the multiplevalues may correspond to a different energy at which the particle beamis output from the particle accelerator.

An example particle therapy system includes a particle accelerator toproduce a particle beam, a scanning magnet to direct the particle beamalong a path at least part-way through the target, and a control systemto control the scanning magnet to direct the particle beam alongmultiple paths at least part-way through the target and to control theenergy of the particle beam so that, along each of the multiple paths,the particle beam treats a three-dimensional columnar portion of thetarget. While the particle beam is directed along each of the multiplepaths, the particle beam delivers a dose of radiation to the target thatexceeds one (1) Gray-per-second for a duration of less than five (5)seconds. The example system may include one or more of the followingfeatures, either alone or in combination.

The control system may be configured to control the scanning magnet sothat the particle beam is directed along each path through the targetonly once. The system may include energy-absorbing structures, each ofwhich may be configured to reduce an energy of the particle beam as theparticle beam passes through the energy-absorbing structure to thetarget. The control system may be configured to control the energy ofthe particle beam by moving one or more of the energy-absorbingstructures into or out of the path of the particle beam between thetarget and a source of the particle beam. The energy-absorbingstructures may include energy-absorbing plates. The control system maybe configured to treat a micro-volume of the target by controlling thescanning magnet to direct the particle beam along multiple paths atleast part-way through the target and to control the energy of theparticle beam so that, along each of the multiple paths, the particlebeam treats a three-dimensional columnar portion of the target.

For a path among the multiple paths along which the particle beam isdirected, the control system may be configured to move the one or moreenergy-absorbing structures into or out of the path of the particle beamwhile the particle beam is at the path. For a path among the multiplepaths, the control system may be configured to move multipleenergy-absorbing structures sequentially into the path of the particlebeam. For a path among the multiple paths, the control system may beconfigured to move multiple energy-absorbing structures sequentially outof the path of the particle beam. An energy-absorbing plate among theenergy absorbing structures may include a linear motor that iscontrollable to move the energy-absorbing plate into or out of the pathof the particle beam. For a path among the multiple paths, the controlsystem may be configured to move each of the one or moreenergy-absorbing structures into or out of the path of the particle beamin a duration of one hundred (100) milliseconds or less. For a pathamong the multiple paths, the control system may be configured to moveeach of the one or more energy-absorbing structures into or out of thepath of the particle beam in a duration of fifty (50) milliseconds orless. For a path among the multiple paths, the control system may beconfigured to move the one or more energy absorbing structures byperforming operations that include controlling a first plate among theone or more energy-absorbing structures to move during passage of theparticle beam through the one or more energy-absorbing structures to thetarget.

The particle accelerator may include superconducting windings. Theparticle accelerator may be configured to produce the particle beambased on a current through the superconducting windings. The controlsystem may be configured to control the energy of the particle beam bysetting the current to one of multiple values. Each of the multiplevalues may correspond to a different energy at which the particle beamis output from the particle accelerator. The control system may beconfigured to control the particle beam to deliver, on each path, a doseof radiation to the target that exceeds twenty (20) Gray-per-second fora duration of less than five (5) seconds. The control system may beconfigured to control the particle beam to deliver, on each path, a doseof radiation to the target that is between twenty (20) Gray-per-secondand one hundred (100) Gray-per-second for a duration of less than five(5) seconds. The control system may be configured to control theparticle beam to deliver, on each path, a dose of radiation to thetarget that is between forty (40) Gray-per-second and one hundred andtwenty (120) Gray-per-second for a specified duration.

The particle beam may be a Gaussian pencil beam having a size of atleast two (2) millimeters sigma. The particle beam may be a Gaussianpencil beam having a size between two (2) millimeters sigma and twenty(20) millimeters sigma.

The particle therapy system may include a collimator that isconfigurable to block a first part of the particle beam while allowing asecond part of the particle beam to reach the target. The collimator mayinclude structures comprised of material to block passage of theparticle beam. The structures may include an edge that moves into thepath of the particle beam such that the first part of the particle beamon a first side of the edge is blocked by the structures and such thatthe second part of the particle beam on a second side of the edge is notblocked by the structures. The collimator may include linear motors thatare controllable to configure the structures to define the edge. Each ofthe linear motors may include a movable component and a stationarycomponent. The stationary component may include a magnetic fieldgenerator to generate a first magnetic field. The movable component mayinclude one or more coils to conduct current to produce a secondmagnetic field that interacts with the first magnetic field to cause themoveable component to move relative to the stationary component. Themovable component of each linear motor may be connected to, or may bepart of, a corresponding one of the structures such that thecorresponding structure moves along with movement with the movablecomponent.

The control system may be configured to control an intensity of theparticle beam along each of the multiple paths. The intensity of theparticle beam may be different along at least two of the multiple paths.

The particle therapy system may include a ridge filter to spread-out aBragg peak of the particle beam. The particle therapy system may includea range modulator wheel to spread-out a Bragg peak of the particle beam.The range modulator wheel may be configured to move in at least twodimensions to track movement of the particle beam. The control systemmay be configured to control an intensity of the particle beam as theparticle beam impacts the range modulator wheel.

In an example, one or more non-transitory machine-readable storage mediastore instructions that are executable to implement an example treatmentplanning system for a particle therapy system. The treatment planningsystem includes a prediction model that characterizes the particletherapy system and a patient to be treated by the particle therapysystem. The prediction model characterizes the particle therapy systemat least in part by characterizing a timing at which the particletherapy system can deliver radiation. The treatment planning system alsoincludes a relative biological effectiveness (RBE) model thatcharacterizes a relative biological effectiveness of the radiation ontissue based on the timing of delivery of the radiation and a dosecalculation engine to determine a dose regimen for delivery of theradiation to voxels of the patient. The dose calculation engine isconfigured to determine the dose regimen based on the prediction modeland the RBE model. The treatment planning system may include one or moreof the following features, either alone or in combination.

The dose regimen may specify doses and dose rates at which the radiationis to be delivered to the voxels. The treatment planning may include asequencer to generate instructions for sequencing delivery of doses inorder to optimize effective doses determined by the dose calculationengine.

The prediction model may characterize the particle therapy system basedon a structure of pulses of a particle beam produced by a particleaccelerator. The prediction model may characterize the particle therapysystem based on a maximum dose per pulse of a particle beam produced bya particle accelerator. The prediction model may characterize theparticle therapy system based on a sweep time of a scanning magnet tomove a particle beam produced by a particle accelerator. The predictionmodel may characterize the particle therapy system based on a time ittakes to change an energy of a particle beam produced by a particleaccelerator. The prediction model may characterize the particle therapysystem based on a time it takes to move one or more energy-absorbingstructures to change an energy of a particle beam produced by a particleaccelerator. The prediction model may characterize the particle therapysystem based on a strategy for regulating doses of radiation. Theprediction model may characterize the particle therapy system based on atime it takes to move a collimator for collimating a particle beamproduced by a particle accelerator. The prediction model maycharacterize the particle therapy system based on a time it takes toconfigure a collimator for collimating a particle beam produced by aparticle accelerator. The prediction model may characterize the particletherapy system based on a time it takes to control a range modulator tochange a Bragg peak of particles in a particle beam produced by aparticle accelerator.

The dose calculation engine may be configured to determine times atwhich doses specified in the dose regimen are to be delivered to thevoxels of the patient based on the RBE model. The dose calculationengine may be configured to determine whether a voxel among the voxelscontains targeted tissue, non-targeted tissue, or both targeted tissueand non-targeted tissue, and to determine a dose rate of radiation tothe voxel based at least in part on whether the voxel contains targetedtissue, non-targeted tissue, or both targeted tissue and non-targetedtissue. The targeted tissue may include diseased tissue and thenon-targeted tissue may include healthy tissue. In a case that the voxelcontains non-targeted tissue only, determining the dose rate ofradiation to the voxel may include determining to deliver no dose to thevoxel. In a case that the voxel contains targeted tissue or bothtargeted tissue and non-targeted tissue, determining the dose rate ofradiation to the voxel may include to deliver ultra-high dose rateradiation to the voxel.

The ultra-high dose rate radiation may include a dose of radiation thatexceeds one (1) Gray-per-second for a duration of less than five (5)seconds. The ultra-high dose rate radiation may include a dose ofradiation that exceeds one (1) Gray-per-second for a duration of lessthan 500 ms. The ultra-high dose rate radiation may include a dose ofradiation that is between 40 Gray-per-second and 120 Gray-per-second fora duration of less than 500 ms.

The dose regimen may specify doses and dose rates at which the radiationis to be delivered to the voxels. The doses may include equivalent dosesdetermined based on a weighting factor from the RBE model. The weightingfactor may cause the dose to increase for a duration.

The sequencer is configured to sequence delivery of the doses based onone or more of the following, based on two or more of the following,based on three or more of the following, based on four or more of thefollowing, based on five or more of the following, or based on all ofthe following: a structure of pulses of a particle beam produced by aparticle accelerator, a maximum dose per pulse of the particle beam, asweep time of a scanning magnet to move the particle beam, a time ittakes to change an energy of the particle beam, a time it takes to moveone or more energy-absorbing structures to change the energy of theparticle beam, a strategy for regulating the doses, a time it takes tomove a collimator for collimating the particle beam, a time it takes toconfigure the collimator, or a time it takes to control a rangemodulator to change a Bragg peak of particles in the particle beam.

For a voxel among the voxels, the sequencer may be configured tosequence delivery of a set of the doses in columns that pass at leastpart-way through the voxel. A voxel may be a micro-volume of anirradiation target to be treated using columns of radiation, may be partof such a micro-volume, or may include multiple such micro-volumes. Eachdose in the set may be delivered at an ultra-high dose rate. For acolumn among the columns, an energy of a particle beam produced by theparticle accelerator may be changed while the particle beam isstationary. The sequence of delivery may be such that, followingtreatment of the column, the particle beam is never again directed totreat the column.

In an example, one or more non-transitory machine-readable storage mediastore instructions that are executable to implement an example treatmentplanning system for a particle therapy system. The treatment planningsystem includes a prediction model that characterizes the particletherapy system and a patient to be treated by the particle therapysystem and a dose calculation engine to determine a dose regimen fordelivery of radiation to voxels of a patient. The dose calculationengine may be configured to determine the dose regimen based on theprediction model. The treatment planning system may include one or moreof the forgoing features, either alone or in combination. The treatmentplanning system may include one or more of the following features,either alone or in combination.

The dose regimen may specify doses and dose rates at which the radiationis to be delivered to the voxels. The treatment planning system mayinclude a sequencer to generate instructions for sequencing delivery ofdoses at rates determined by the dose calculation engine.

An example method includes storing, in computer memory, firstinformation that characterizes a particle therapy system and a patientto be treated by the particle therapy system. The method includesstoring, in computer memory, second information that characterizes arelative biological effectiveness of radiation on tissue. The methodalso includes determining, by one or more processing devices, a doseregimen for delivery of the radiation to voxels of the patient. The doseregimen may be determined based on the first information and the secondinformation. The method may include one or more of the followingfeatures, either alone or in combination.

The dose regimen may specify doses and dose rates at which the radiationis to be delivered to the voxels. The method may include generatinginstructions for sequencing delivery of doses at rates specified in thedose regimen.

The first information may characterize the particle therapy system basedon a structure of pulses of a particle beam produced by a particleaccelerator. The first information may characterize the particle therapysystem based on a maximum dose per pulse of a particle beam produced bya particle accelerator. The first information may characterize theparticle therapy system based on a sweep time of a scanning magnet tomove a particle beam produced by a particle accelerator. The firstinformation may characterize the particle therapy system based on a timeit takes to change an energy of a particle beam produced by a particleaccelerator. The first information may characterize the particle therapysystem based on a time it takes to move one or more energy-absorbingstructures to change an energy of a particle beam produced by a particleaccelerator. The first information may characterize the particle therapysystem based on a strategy for regulating the doses. The firstinformation may characterize the particle therapy system based on a timeit takes to move a collimator for collimating a particle beam producedby a particle accelerator. The first information may characterize theparticle therapy system based on a time it takes to configure acollimator for collimating a particle beam produced by a particleaccelerator. The first information may characterize the particle therapysystem based on a time it takes to control a range modulator to change aBragg peak of particles in a particle beam produced by a particleaccelerator.

Determining the dose regimen may include determining times at whichdoses specified in the dose regimen are to be delivered to the voxels ofthe patient based on the second information. Determining the doseregimen may include determining whether a voxel among the voxelscontains targeted tissue, non-targeted tissue, or both targeted tissueand non-targeted tissue, and determining a dose rate of radiation to thevoxel based at least in part on whether the voxel contains targetedtissue, non-targeted tissue, or both targeted tissue and non-targetedtissue. The targeted tissue may include diseased tissue and thenon-targeted tissue may include healthy tissue. In a case that the voxelcontains non-targeted tissue only, determining the dose rate ofradiation to the voxel may include determining to deliver no dose to thevoxel. In a case that the voxel contains targeted tissue or bothtargeted tissue and non-targeted tissue, determining the dose rate ofradiation to the voxel may include determining to deliver ultra-highdose rate radiation to the voxel.

The ultra-high dose rate radiation may include a dose of radiation thatexceeds one (1) Gray-per-second for a duration of less than five (5)seconds. The ultra-high dose rate radiation may include a dose ofradiation that exceeds one (1) Gray-per-second for a duration of lessthan 500 ms. The ultra-high dose rate radiation may include a dose ofradiation that is between 40 Gray-per-second and 120 Gray-per-second fora duration of less than 500 ms.

The dose regimen may specify doses and dose rates at which the radiationis to be delivered to the voxels. The doses may include equivalent dosesdetermined based on a weighting factor from the second information. Theweighting factor may cause the dose to increase for a duration.

Sequencing delivery of doses is based on one or more of the following,two or more of the following, three or more of the following, four ormore of the following, five or more of the following, or all of thefollowing: a structure of pulses of a particle beam produced by aparticle accelerator, a maximum dose per pulse of the particle beam, asweep time of a scanning magnet to move the particle beam, a time ittakes to change an energy of the particle beam, a time it takes to moveone or more energy-absorbing structures to change the energy of theparticle beam, a strategy for regulating the doses, a time it takes tomove a collimator for collimating the particle beam, a time it takes toconfigure the collimator, or a time it takes to control a rangemodulator to change a Bragg peak of particles in the particle beam.

For a voxel among the voxels, sequencing delivery of doses may includesequencing delivery of a set of the doses in columns that pass at leastpart-way through the voxel. Each dose in the set may be delivered at anultra-high dose rate. For a column among the columns, an energy of aparticle beam produced by a particle accelerator may be changed whilethe particle beam is stationary. The sequence of delivery may be suchthat, following treatment of the column, the particle beam is neveragain directed to treat the column.

An example method includes storing, in computer memory, firstinformation that characterizes a particle therapy system and a patientto be treated by the particle therapy system; and determining, by one ormore processing devices, a dose regimen for delivery of radiation tovoxels of a patient. The dose regimen may be determined based on thefirst information. The method may include one or more of the followingfeatures, either alone or in combination.

The dose regimen may specify doses and dose rates at which the radiationis to be delivered to the voxels. The method may include generatinginstructions for sequencing delivery of doses at rates specified in thedose regimen.

An example system includes a particle accelerator to produce radiationfor delivery to a patient; a scanning system to control the delivery ofthe radiation to the patient; a treatment planning system to generate atreatment plan that specifies how to deliver the radiation to voxels ofthe patient; and a control system to control the particle acceleratorand the scanning system to deliver the radiation to the voxels of thepatient in accordance with the treatment plan.

The treatment planning system may be programmed to generate thetreatment plan by performing the following operations: storing, incomputer memory, first information that characterizes a particle therapysystem and a patient to be treated by the particle therapy system;storing, in computer memory, second information that characterizes arelative biological effectiveness of radiation on tissue; anddetermining, by one or more processing devices, a dose regimen fordelivery of the radiation to voxels of the patient, where the doseregimen is determined based on the first information and the secondinformation.

The treatment planning system may be programmed to generate thetreatment plan by performing the following operations: storing, incomputer memory, first information that characterizes a particle therapysystem and a patient to be treated by the particle therapy system; anddetermining, by one or more processing devices, a dose regimen fordelivery of radiation to voxels of a patient, where the dose regimen isdetermined based on the first information.

The treatment planning system may include a prediction model thatcharacterizes the particle therapy system and a patient to be treated bythe particle therapy system. The prediction model characterizes theparticle therapy system at least in part by characterizing a timing atwhich the particle therapy system can deliver radiation. The treatmentplanning system also includes a relative biological effectiveness (RBE)model that characterizes a relative biological effectiveness of theradiation on tissue based on the timing of delivery of the radiation anda dose calculation engine to determine a dose regimen for delivery ofthe radiation to voxels of the patient. The dose calculation engine isconfigured to determine the dose regimen based on the prediction modeland the RBE model.

The treatment planning may also include a sequencer to generateinstructions for sequencing delivery of doses in order to optimizeeffective doses determined by the dose calculation engine.

The treatment planning system may include a prediction model thatcharacterizes the particle therapy system and a patient to be treated bythe particle therapy system, and a dose calculation engine to determinea dose regimen for delivery of radiation to voxels of a patient. Thedose calculation engine may be configured to determine the dose regimenbased on the prediction model.

The treatment planning may also include a sequencer to generateinstructions for sequencing delivery of doses in order to optimizeeffective doses determined by the dose calculation engine.

The treatment planning system may include a first computing system, thecontrol system may include a second computing system, and the firstcomputing system may be different from the second computing system. Thetreatment planning system and the control system may be implemented on asame computing system. The example system may include any of thefeatures described herein including, but not limited to, those set forthin this summary section above.

Two or more of the features described in this disclosure, includingthose described in this summary section, may be combined to formimplementations not specifically described herein.

Control of the various systems described herein, or portions thereof,may be implemented via a computer program product that includesinstructions that are stored on one or more non-transitorymachine-readable storage media and that are executable on one or moreprocessing devices (e.g., microprocessor(s), application-specificintegrated circuit(s), programmed logic such as field programmable gatearray(s), or the like). The systems described herein, or portionsthereof, may be implemented as an apparatus, method, or electronicsystem that may include one or more processing devices and computermemory to store executable instructions to implement control of thestated functions.

The details of one or more implementations are set forth in theaccompanying drawings and the description below. Other features,objects, and advantages will be apparent from the description anddrawings, and from the claims.

DESCRIPTION OF THE DRAWINGS

FIG. 1 is a perspective view of an example irradiation target treated byscanning a particle beam across entire layers sequentially.

FIG. 2 is a perspective view of an example irradiation target treated byscanning a particle beam column-by-column across the target.

FIG. 3 is a cut-away view of part of an example particle acceleratorthat is usable in the particle therapy system described herein.

FIG. 4 is a side view of components of an example scanning system thatis usable in the particle therapy system described herein.

FIG. 5 is a perspective view of components of the example scanningsystem that is usable in the particle therapy system described herein.

FIG. 6 is a front view of an example magnet for use in a scanning systemof the type shown in FIGS. 4 and 5 .

FIG. 7 is a perspective view of an example magnet for use in a scanningsystem of the type shown in FIGS. 4 and 5 .

FIG. 8 is a perspective view of an example energy degrader (rangemodulator) for use in a scanning system of the type shown in FIGS. 4 and5 .

FIG. 9 is a perspective view of a process for moving a plate of theenergy degrader into and out of the path of a particle beam.

FIG. 10 is a block diagram of example linear motors and example platesof an energy degrader controlled thereby.

FIG. 11 is a flowchart showing an example process for treating anirradiation target by scanning a particle beam column-by-column acrossthe target.

FIGS. 12, 13, 14, and 15 are perspective block diagrams illustratingtreatment of a column of an irradiation target by movingenergy-absorbing plates sequentially into a path of a stationaryparticle beam.

FIGS. 16, 17, 18, and 19 are perspective block diagrams illustratingtreatment of a column of an irradiation target by movingenergy-absorbing plates sequentially out of a path of a stationaryparticle beam.

FIG. 20 is a perspective view of an example configurable collimator leafthat is usable with the example configurable collimators describedherein.

FIG. 21 is a top view of configurable collimator leaves positionedrelative to a treatment area of an irradiation target.

FIG. 22 is a perspective view of an example configurable collimator.

FIG. 23 is a front view of the example configurable collimator.

FIG. 24 is a perspective, view of the example configurable collimatorhaving components portrayed in see-through to show the interiorsthereof.

FIG. 25 is a perspective view of the example configurable collimatorpositioned relative to a patient during particle therapy treatment.

FIGS. 26 and 27 are front and perspective views, respectively, of anexample particle therapy system.

FIG. 28 is a perspective view of an example particle therapy system.

FIG. 29 is a graph showing changes in particle beam spot size fordifferent particle beam energies for different materials used in theenergy degrader to change the energy of the particle beam.

FIG. 30 is a block diagram showing components of an example treatmentplanning system.

FIG. 31 is a cross-sectional view of voxels in a patient.

FIG. 32 is a diagram showing an example spread-out Bragg peak (SOBP) anda column that is part of example irradiation target.

FIGS. 33 to 42 are perspective block diagrams illustrating exampleprocesses for treating columns of an irradiation target by micro-volume.

FIGS. 43A and 43B are plots showing results of Monte Carlo simulationsthat calculate radiation dose delivered to a treatment volume and thetime it takes for each voxel in that dose calculation to reach a finaldose.

Like reference symbols in the various drawings indicate like elements.

DETAILED DESCRIPTION

Described herein are example implementations of a treatment planningsystem for a particle therapy system. An example treatment planspecifies a dose regimen for treating a patient using radiation. Thedose regimen may include doses to be delivered, rates at which doses areto be delivered called “dose rates”, or both doses to be delivered anddose rates. A dose in a dose regimen may include simply an amount ofradiation deposited during treatment. A dose in a dose regimen mayinclude a biological equivalent dose, also called “equivalent dose”. Abiological equivalent dose may include an amount of radiation outputthat is needed to treat diseased tissue in the patient accounting forbiological effects of tissue in the patient on the radiation deposited.In some implementations, the treatment planning system may be used togenerate instructions to apply dose rates of radiation tothree-dimensional treatment volumes within a patient called voxels. Allor part of the treatment planning system may be implemented byexecuting, on one or more processing devices, one or more computerprograms that are stored on, and retrieved from, one or morenon-transitory machine-readable storage media.

The example treatment planning system and its variations describedherein may be used to generate instructions to apply ultra-high doserates of radiation—so called, “FLASH” dose rates of radiation—to anirradiation target. In this regard, experimental results in radiationtherapy have shown an improvement in the condition of healthy tissuesubjected to radiation when the treatment dose is delivered atultra-high (FLASH) dose rates. In an example, when delivering doses ofradiation at 10 to 20 Gray (Gy) in pulses of less than 500 milliseconds(ms) reaching effective dose rates of 20 to 100 Gray-per-second (Gy/S),healthy tissue experiences less damage than when irradiated with thesame dose over a longer time scale, while tumors are treated withsimilar effectiveness. A theory that may explain this “FLASH effect” isbased on the fact that radiation damage to tissue is proportionate tooxygen supply in the tissue. In healthy tissue, the ultra-high dose rateradicalizes the oxygen only once, as opposed to dose applications thatradicalize the oxygen multiple times over a longer timescale. This maylead to less damage in the healthy tissue using the ultra-high doserate.

In an example, the treatment planning system includes a predictive,accelerator-dependent timing model called the “prediction model”, atime-dependent relative biological effectiveness (RBE) model, a dosecalculation engine that incorporates time-dependent RBE effects that mayoccur by delivering the radiation at ultra-high dose (FLASH) rates forexample, and a sequencer or optimizer that sequences particle beamdelivery to generate optimized ultra-high dose rate (or other) doseregimens. In this example, the treatment planning system is implementedat least in part using software and is configured—for example, writtenor programmed—to determine, for a proposed beam delivery, the times atwhich any dose is delivered to any given volume in an irradiationtarget.

The prediction model characterizes or models components of the particletherapy system that delivers radiation to a patient. For example, theprediction model may characterize components of a particle therapysystem including the system's ability to deliver a sequence of spots orcolumns of radiation in a time required to provide an ultra-high dose ofradiation. The prediction model may also characterize or model thepatient and the treatment target, such as a tumor in the patient. Theprediction model may be implemented using one or more computerprogramming objects; a data structure such as one or more look-up tables(LUTs), arrays, lists, or binary trees; or any appropriate softwaremodel.

The RBE model characterizes the relative biological effectiveness ofradiation on tissue in a time-dependent manner. In other words, the RBEmodel characterizes a relative biological effectiveness of radiation ontissue based on a timing of radiation delivery to that tissue. Forexample, when radiation is applied at ultra-high (FLASH) dose rates,healthy tissue may experience less damage than when that same tissue isirradiated with the same dose over a longer time scale, while tumors aretreated with similar effectiveness. In other words, for tumors or otherdiseased tissue, a critical factor for treatment is total radiation doseas opposed to dose rate, whereas for healthy tissue, dose rate is afactor in reducing damage where no damage is desired. The RBE model mayinclude information about different types of healthy and diseasedtissues and the effects different dose rates of radiation have on thosedifferent types of tissues. The RBE model may include information abouthow different types of healthy and diseased tissues affect the deliveryand absorption of the radiation. The RBE model may also include theeffects that different types or radiation have on different types oftissues at different dose rates. The RBE model may be implemented usingone or more computer programming objects; a data structure such as oneor more look-up tables (LUTs), arrays, lists, or binary trees; or anyappropriate software models.

The dose calculation engine determines the dose regimen for a patient.For example, the dose calculation engine may determine doses of theradiation to deliver to voxels in the patient and the rates at whichthose doses are to be delivered. The dose calculation engine usesinformation from the prediction model and the RBE model in performingits calculations. In this regard, the dose calculation engine isconfigured—for example, written or programmed—to determine the doses anddose rates based at least in part on the time-dependent RBE of theradiation to tissue in the patient. Thus, the dose calculation enginemay identify whether that tissue in the patient is healthy or diseased,use the RBE model and the prediction model to calculate the durationover which a dose or doses of radiation is/are to be delivered to thattissue based on system constraints, and scale dose to the target tissuebased on the desired type of treatment. For example, the dosecalculation engine may be configured to identify a target within thepatient such as a malignant neoplasm and also to identify healthy tissuein the patient. The dose calculation engine may then determine the RBEof radiation on that tissue based on the RBE model. The dose calculationengine may then determine the doses of radiation to deliver to thetarget and the rates at which the doses are to be delivered given theconstraints of the system delivering the dose and any relevant patientinformation based on the prediction model. To the extent possible, thedose calculation engine avoids delivery of radiation to the healthytissue, while maintaining appropriate dosage such as ultra-high doserates to voxels that make up the target. To the extent that radiationimpacts healthy tissue, delivering that radiation at ultra-high (FLASH)dose rates may make that impact less damaging to the healthy tissue thanis the case in traditional applications at lower dose rates.

Using a combination of the prediction model, the RBE model, and the dosecalculation engine, all of which take timing into account in one way oranother, the treatment planning system can generate time-dependenttreatment plans with appropriate dose regimens, and a user can evaluatetheir quality. A beam delivery sequence may be created or modifiedmanually using a forward planning approach to produce a sequencedtreatment plan that takes advantage of the FLASH effect. For example, auser may manually arrange the delivery of radiation into columns havinga constant beam steering or choose beam angles or collimation thatreduces the degree of overlap between different columns of radiation.

The sequencer or optimizer may be configured—for example, written orprogrammed—to generate instructions, such as computer-executableinstructions, for sequencing delivery of the doses at rates determinedby the dose calculation engine. The treatment planning system may usethe sequencer or optimizer to perform sequence optimizationautomatically by sequencing the treatment using an inverse planningapproach. In an example, the sequencer uses the sequence of beam or spotdelivery as additional degrees of freedom and uses optimizationtechniques to determine the sequence that best achieves input criteriaspecified by the user while accounting for time-dependent effects.

As stated, the sequencer may employ inverse planning to determine thesequence in which the doses of radiation are to be delivered. In someimplementations, inverse planning includes obtaining target dosedistributions of radiation and then performing a process, such as anoptimization process, to determine how to deliver that radiation toachieve the objectives of the treatment plan—for example, to destroymalignant tissue—under the time constraints required to achieveultra-high (FLASH) dose rates. In an example, given characteristics inthe prediction model and the target dosage, the sequencer may determinethat radiation is to be applied to voxels of the patient in columns. Thesequencer may determine the radius and length of those columns, wherethose columns should be located in the target, and the order in whicheach column of radiation is to be delivered. In an example that does notuse ultra-high dose rates, the sequencer may determine that radiation isto be applied in spots to layers of the target. The sequencer maydetermine the size, shape, and locations of the spots, the thickness ofthe layers, the number of layers, the number of protons in each spot,the order in which each spot is to be applied, and the order in whichthe layers are to be treated.

In some implementations, the sequencer is configured to sequencedelivery of the doses based on one or more of the following, two or moreof the following, three or more of the following, four or more of thefollowing, five or more of the following, or all of the following: astructure of pulses of a particle beam produced by the particleaccelerator, a maximum dose per pulse of the particle beam, a sweep timeof a scanning magnet to move the particle beam, a time it takes tochange an energy of the particle beam, a time it takes to move one ormore energy-absorbing structures to change the energy of the particlebeam, a strategy for regulating the doses, a time it takes to move acollimator for collimating the particle beam, a time it takes toconfigure the collimator, or a time it takes to control a rangemodulator to change a Bragg peak of particles in the particle beam.

The treatment planning system may be used with particle therapy systemsfor treating an irradiation target (or simply, “target”), such as atumor, using a particle beam such as a proton or ion beam. In thisregard, some such systems treat the target cross-sectional layer bylayer. For example, the energy of the particle beam may be controlled todeliver a radiation dose (or simply, “dose”) to a layer and then theparticle beam may be moved across all or part of that layer. Thereafter,the energy of the particle beam may be changed to deliver dose toanother layer. The particle beam may be moved across all or part of thatother layer and so on until the entire target is treated. For example,FIG. 1 shows treating an entire layer 10 of a target 11 using a particlebeam 12 having an energy sufficient to deliver dose to layer 10 bymoving the particle beam across the layer along the directions of arrows15. Then a different layer 16 of the target 11 is treated in the samemanner using a particle beam having a different energy sufficient todeliver dose to layer 16, and so on. The treatment of each layer istypically at relatively average dose rates, such as 0.1 Gray-per-second.The particle beam often penetrates healthy tissue before reaching thetarget. Any one location within this healthy tissue may be visitedseveral times over the course of treatment. The dose at such a locationis received over a time scale on the order of minutes.

By contrast, particle therapy systems may treat three-dimensionalcolumns of the target using ultra-high dose rate radiation—the FLASHdoses of radiation. These systems scale the ultra-high dose ratedeliveries to targets using pencil beam scanning. In some examples,pencil beam scanning includes delivering a series of small beams ofparticle radiation that can each have a unique direction, energy, andcharge. By combining doses from these individual beams, athree-dimensional target treatment volume may be treated with radiation.Furthermore, instead of organizing the treatment into layers at constantenergies, the systems organize the treatment into columns defined by thedirection of a stationary beam. The direction of the beam may be towardthe surface of the target.

In some implementations, all or part of a column is treated before theparticle beam is directed along another path through the irradiationtarget. In some implementations, a path through the target is all orpart-way through the target. In an example, the particle beam may bedirected along a path through a target and not deviate from that path.While directed along that path, the energy of the particle beam ischanged. The particle beam does not move as its energy changes and, as aresult, the particle beam treats all or a part of an interior portion ofthe target that extends along a length of the particle beam and along awidth of the beam spot. The treatment is thus depth-wise along alongitudinal direction of the beam. For example, a portion of the targettreated may extend from a spot of the beam at the surface of the targetdown through all or part of an interior of the target. The result isthat the particle beam treats a three-dimensional columnar portion ofthe target using an ultra-high dose rate of radiation. In some examples,ultra-high dose rates of radiation include, for example, doses ofradiation that exceed 1 Gray-per-second for a duration of less than 500milliseconds (ms), that exceed 1 Gray-per-second for a duration ofbetween 10 ms and 5 seconds (s), or that exceed 1 Gray-per-second for aduration of less than 5 s. Other examples are provided herein.

In some implementations, after a column of the target has been treatedas described in the preceding paragraph, the particle beam is directedalong a new, different path through the target. For example, as shown inFIG. 2 , a column 20 of target 21 is treated by varying the energy of aparticle beam 22 that proceeds along the direction of arrow 28. Theparticle beam is then directed along a new path 24 through target 21where it proceeds along the direction of arrow 29. A column 25 is thentreated along that new path by varying the energy of the particle beamwhile the particle beam is stationary. As noted, the column is locatedalong the longitudinal extent of the beam. In some implementations, theparticle beam is directed along each path through the target only oncewhen treating columns of the target.

As a result of the foregoing protocol, healthy tissue above or belowtarget 21 is exposed to the ultra-high dose rate of radiation once andnot to multiple low doses of radiation as occurs when targets aretreated layer-by-layer as in FIG. 1 . Accordingly, in someimplementations the particle beam is directed along a new path andupstream tissue along that path is never visited again. In this way,each location within the target can be treated at a rate that iscomparable to that of an individual pencil beam modulated with the layerswitching time. The average dose rate over the entire treatment may becomparable to layer-by-layer radiation deliveries, but the localizeddose rate for any one spot is at an ultra-high dose rate.

In some cases, a reduction in damage to healthy tissue may occur whenradiation is delivered at ultra-high dose rates. For example, whendelivering radiation doses of 10 to 20 Gray in pulses of less than 500ms—reaching effective dose rates of 20 to 100 Gray-per-second—healthytissue may be less damaged than when irradiated with the same dose overa longer time scale, while the delivered radiation may treat tumors withthe same level of effectiveness.

In some implementations, in order to achieve ultra-high dose rates, theenergy of the particle beam may be changed at a rate that exceedschanges of energy used for layer-by-layer scanning. For example,ultra-high dose rates applied to columns of a target may be achieved byswitching beam energy in a duration of 50 ms. For example, ultra-highdose rates applied to columns of a target may be achieved by switchingbeam energy in a duration of 10 ms or less. This may be achieved, forexample, by controlling motion of the particle beam and motion ofenergy-absorbing plates or other structures into and out of the path ofthe particle beam. By way of example, a 5 centimeter (cm) deep column,which might require 5 layer switches, may require 250 ms of down-timeduring which particle beam is not delivered, allowing 250 ms of beamdelivery during which 10 to 20 Gray of dose may be delivered. Fastermotion of the energy-absorbing plates and/or additional coordination ofbeam motion may further decrease the layer switching time allowing evenmore time to deliver the required treatment dose while still meeting therequirement for a localized ultra-high dose rate.

Described below are example implementations of a particle therapy systemconfigured to deliver radiation at ultra-high dose rates throughthree-dimensional columns of a target in accordance with a treatmentplan determined by a treatment planning system. In an exampleimplementation, the particle therapy system is a proton therapy system.As described herein, an example proton therapy system scans a protonbeam in three dimensions across an irradiation target in order todestroy malignant tissue. FIG. 3 shows a cross-section of components 310of an example superconducting synchrocyclotron that may be used toprovide a particle (e.g., a proton) beam in the proton therapy system.In this example, components 310 include a superconducting magnet 311.The superconducting magnet includes superconducting coils 312 and 313.The superconducting coils are formed of multiple integrated conductors,each of which includes superconducting strands—for example, four strandsor six strands—wound around a center strand which may itself besuperconducting or non-superconducting. Each of the superconductingcoils 312, 313 is for conducting a current that generates a magneticfield (B). The magnetic yokes 314, 315 or smaller magnetic pole piecesshape that magnetic field in a cavity 316 in which particles areaccelerated. In an example, a cryostat (not shown) uses liquid helium(He) to conductively cool each coil to superconducting temperatures,e.g., around 4° Kelvin (K).

In some implementations, the particle accelerator includes a particlesource 317, such as a Penning Ion Gauge—PIG source, to provide anionized plasma column to cavity 316. Hydrogen gas, or a combination ofhydrogen gas and a noble gas, is ionized to produce the plasma column. Avoltage source provides a varying radio frequency (RF) voltage to cavity316 to accelerate particles from the plasma column within the cavity. Asnoted, in an example, the particle accelerator is a synchrocyclotron.Accordingly, the RF voltage is swept across a range of frequencies toaccount for relativistic effects on the particles, such as increasingparticle mass, when accelerating particles within the accelerationcavity. The RF voltage drives a dee plate contained within the cavityand has a frequency that is swept downward during the accelerating cycleto account for the increasing relativistic mass of the protons and thedecreasing magnetic field. A dummy dee plate acts as a ground referencefor the dee plate. The magnetic field produced by running currentthrough the superconducting coils, together with sweeping RF voltage,causes particles from the plasma column to accelerate orbitally withinthe cavity and to increase in energy as a number of turns increases.

The magnetic field in the cavity is shaped to cause particles to moveorbitally within the cavity. The example synchrocyclotron employs amagnetic field that is uniform in rotation angle and falls off instrength with increasing radius. In some implementations, the maximummagnetic field produced by the superconducting (main) coils may bewithin the range of 4 Tesla (T) to 20T at a center of the cavity, whichfalls off with increasing radius. For example, the superconducting coilsmay be used in generating magnetic fields at, or that exceed, one ormore of the following magnitudes: 4.0T, 4.1T, 4.2T, 4.3T, 4.4T, 4.5T,4.6T, 4.7T, 4.8T, 4.9T, 5.0T, 5.1T, 5.2T, 5.3T, 5.4T, 5.5T, 5.6T, 5.7T,5.8T, 5.9T, 6.0T, 6.1T, 6.2T, 6.3T, 6.4T, 6.5T, 6.6T, 6.7T, 6.8T, 6.9T,7.0T, 7.1T, 7.2T, 7.3T, 7.4T, 7.5T, 7.6T, 7.7T, 7.8T, 7.9T, 8.0T, 8.1T,8.2T, 8.3T, 8.4T, 8.5T, 8.6T, 8.7T, 8.8T, 8.9T, 9.0T, 9.1T, 9.2T, 9.3T,9.4T, 9.5T, 9.6T, 9.7T, 9.8T, 9.9T, 10.0T, 10.1T, 10.2T, 10.3T, 10.4T,10.5T, 10.6T, 10.7T, 10.8T, 10.9T, 11.0T, 11.1T, 11.2T, 11.3T, 11.4T,11.5T, 11.6T, 11.7T, 11.8T, 11.9T, 12.0T, 12.1T, 12.2T, 12.3T, 12.4T,12.5T, 12.6T, 12.7T, 12.8T, 12.9T, 13.0T, 13.1T, 13.2T, 13.3T, 13.4T,13.5T, 13.6T, 13.7T, 13.8T, 13.9T, 14.0T, 14.1T, 14.2T, 14.3T, 14.4T,14.5T, 14.6T, 14.7T, 14.8T, 14.9T, 15.0T, 15.1T, 15.2T, 15.3T, 15.4T,15.5T, 15.6T, 15.7T, 15.8T, 15.9T, 16.0T, 16.1T, 16.2T, 16.3T, 16.4T,16.5T, 16.6T, 16.7T, 16.8T, 16.9T, 17.0T, 17.1T, 17.2T, 17.3T, 17.4T,17.5T, 17.6T, 17.7T, 17.8T, 17.9T, 18.0T, 18.1T, 18.2T, 18.3T, 18.4T,18.5T, 18.6T, 18.7T, 18.8T, 18.9T, 19.0T, 19.1T, 19.2T, 19.3T, 19.4T,19.5T, 19.6T, 19.7T, 19.8T, 19.9T, 20.0T, 20.1T, 20.2T, 20.3T, 20.4T,20.5T, 20.6T, 20.7T, 20.8T, 20.9T, or more. Furthermore, thesuperconducting coils may be used in generating magnetic fields that areoutside the range of 4T to 20T or that are within the range of 4T to 20Tbut that are not specifically listed herein.

In some implementations, such as the implementations shown in FIG. 3 ,the relatively large ferromagnetic magnetic yokes 314, 315 act asreturns for stray magnetic fields produced by the superconducting coils.In some systems, a magnetic shield (not shown) surrounds the yokes. Thereturn yokes and the shield together act to reduce stray magneticfields, thereby reducing the possibility that stray magnetic fields willadversely affect the operation of the particle accelerator.

In some implementations, the return yokes and shield may be replaced by,or augmented by, an active return system. An example active returnsystem includes one or more active return coils that conduct current ina direction opposite to current through the main superconducting coils.In some example implementations, there is an active return coil for eachsuperconducting main coil, e.g., two active return coils—one for eachmain superconducting coil. Each active return coil may also be asuperconducting coil that surrounds the outside of a corresponding mainsuperconducting coil concentrically.

By using an active return system, the relatively large ferromagneticmagnetic yokes 314, 315 can be replaced with magnetic pole pieces thatare smaller and lighter. Accordingly, the size and weight of thesynchrocyclotron can be reduced further without sacrificing performance.An example of an active return system that may be used is described inU.S. Pat. No. 8,791,656 entitled “Active Return System”, the contents ofwhich are incorporated herein by reference.

At or near the output of an extraction channel of the particleaccelerator, there may be one or more beam shaping elements including ascanning system. Components of the scanning system may be mounted on, orotherwise attached to, a nozzle for positioning relatively close to thepatient during treatment.

Referring to FIG. 4 , in an example implementation, at the output ofextraction channel 420 of synchrocyclotron 421 (which may have theconfiguration of FIG. 3 ) are example scanning components 422 that maybe used to move the particle beam three-dimensionally over and throughan irradiation target. FIG. 5 also shows examples of the components ofFIG. 4 . These include, but are not limited to, one or more scanningmagnets 424, an ion chamber 425, an energy degrader 426, and aconfigurable collimator 428. Some implementations may not include aconfigurable collimator. In example implementations such as these, theparticle beam passes through the energy degrader and to the patientwithout subsequent conditioning such as collimation. Other componentsthat may be down-beam of the extraction channel are not shown in FIG. 4or 5 and may include, for example, one or more scattering devices forchanging beam spot size. An example scattering device includes a plateor range modulator that disperses the particle beam as the particle beampasses through the scattering device.

In an example operation, scanning magnet 424 is controllable in twodimensions (e.g., Cartesian XY dimensions) to position the particle beamin those two dimensions and to move the particle beam across at least apart of an irradiation target. Ion chamber 425 detects the dosage of thebeam and feeds-back that information to a control system to adjust beammovement. Energy degrader 426 is controllable to move structures into,and out of, the path of the particle beam to change the energy of theparticle beam and therefore the depth to which dose of the particle beamwill be deposited in the irradiation target. Examples of such structuresinclude, but are not limited to, energy-absorbing plates; polyhedra suchas wedges, tetrahedra, or toroidal polyhedra; and curvedthree-dimensional shapes, such as cylinders, spheres, or cones. In thisway, the energy degrader can cause the particle beam to deposit doses ofradiation in the interior of an irradiation target to treat columns ofthe target. In this regard, when protons move through tissue, theprotons ionize atoms of the tissue and deposit a dose along their path.The Bragg peak is a pronounced peak on the Bragg curve which plots theenergy loss of ionizing radiation during its travel through tissue. TheBragg peak represents the depth at which most protons deposit withintissue. For protons, the Bragg peak occurs right before the particlescome to rest. Accordingly, the energy of the particle beam may bechanged to change the location of its Bragg peak and, therefore, where amajority of the dose of protons will deposit in depth in the tissue.

FIGS. 6 and 7 show views of an example scanning magnet 424. In thisexample, scanning magnet 424 includes two coils 441, which controlparticle beam movement in the X dimension, and two coils 442, whichcontrol particle beam movement in the Y dimension. Control is achieved,in some implementations, by varying current through one or both sets ofcoils to thereby vary the magnetic field(s) produced thereby. By varyingthe magnetic field(s) appropriately, the particle beam can be moved inthe X and/or Y dimension across the irradiation target. The energydegrader described previously can move the beam in the Z dimensionthrough the target, thereby enabling scanning in three dimensions.

Referring back to FIG. 4 , a current sensor 427 may be connected to, orbe otherwise associated with, scanning magnet 424. For example, thecurrent sensor may be in communication with, but not connected to, thescanning magnet. In some implementations, the current sensor samplescurrent applied to magnet 424, which may include current to the coil(s)for controlling beam scanning in the X dimension and/or current to thecoil(s) for controlling beam scanning in the Y dimension. The currentsensor may sample current through the magnet at times that correspond tothe occurrence of pulses in the particle beam or at a rate that exceedsthe rate that the pulses occur in the particle beam. The samples, whichidentify the magnet current, are correlated to detection of the pulsesby the ion chamber described below. For example, the times at whichpulses are detected using the ion chamber may be correlated in time tosamples from the current sensor, thereby identifying the current in themagnet coil(s) at the times of the pulses. Using the magnet current, itthus may be possible to determine the location within the irradiationtarget where each pulse, and thus dose of radiation—that is, dose ofparticles—was delivered. The location of the dose delivered within thetarget may also be determined based on the configuration of the energydegrader, for example, based on the number of plates in the beam path.

During operation, the magnitude value of the magnet current may bestored for each location at which a dose is delivered, along with theamount (e.g., intensity) of the dose. A control system, which may beeither on the accelerator or remote from the accelerator and which mayinclude memory and one or more processing devices, may correlate themagnet current to coordinates within the irradiation target, and thosecoordinates may be stored along with the amount of the dose. Forexample, the location may be identified by depth-wise layer number andCartesian XY coordinates or by Cartesian XYZ coordinates, with thedepth-wise layer corresponding to the Z coordinate. In someimplementations, both the magnitude of the magnet current and thecoordinate locations may be stored along with the dose at each location.This information may be stored in memory either on, or remote from, theaccelerator. This information may be used to track treatment of thetarget and to maintain a record of that treatment.

Ion chamber 425 detects dosage, such as one or more individual doses,applied by the particle beam to positions within the irradiation targetby detecting the numbers of ion pairs created within a gas caused byincident radiation. The numbers of ion pairs correspond to the doseprovided by the particle beam. That information is fed-back to thecontrol system and stored in memory along with the time that the dose isprovided. This information may be correlated to, and stored inassociation with, the location at which the dose was provided and/or themagnitude of the magnet current at that time, as described above.

As noted previously, some implementations do not include a configurablecollimator. In example implementations that include a configurablecollimator, configurable collimator 428 may be located down-beam of thescanning magnets and down-beam of the energy degrader, as shown in FIGS.4 and 5 . The configurable collimator may trim the particle beam on aspot-by-spot basis during movement of the particle beam from path topath through the target. The configurable collimator may also trim theparticle beam while the particle beam is stationary on the target andwhen the energy of the stationary particle beam changes to impactdifferent portions of the interior of the target. For example, theparticle beam may spread along its diameter as it enters the interior ofthe target. That spread may change for different depths within theinterior. The collimator may be configured to trim the particle beam toaccount for that spread. For example, the collimator may be configuredand reconfigured so that the diameter or size of the spot remains thesame for the entirety of a column being treated.

In some implementations, the configurable collimator may include sets ofleaves that face each other and that are movable into and out ofcarriages to create an aperture shape. Parts of the particle beam thatexceed the aperture shape are blocked, and do not pass to the patient.The parts of the beam that pass to the patient are at least partlycollimated, thereby providing a beam with a relatively precise edge. Insome implementations, each leaf in a set of leaves disposed, forexample, on a carriage in the configurable collimator is controllableusing a single linear motor to define an edge that is movable into apath of the particle beam such that a first part of the particle beam ona first side of the edge is blocked by the multiple leaves and such thata second part of the particle beam on a second side of the edge is notblocked by the multiple leaves. The leaves in each set are individuallycontrollable during scanning to trim an area as small as a single spot,and can also be used to trim larger multi-spot areas. The ability totrim a single spot may be significant when treating a column of atarget, since different amounts of trimming may need to be performed fordifferent particle beam energies.

FIG. 8 shows an example range modulator 460, which is an exampleimplementation of energy degrader 426. In some implementations, rangemodulator 460 may be located down-beam of the scanning magnets betweenthe configurable collimator and the patient. In some implementations,such as that shown in FIG. 8 , the range modulator includes a series ofplates 461. The plates may be made of one or more of the followingexample materials: polycarbonate such as LEXAN™ carbon, beryllium, boroncarbide, a composite material comprised of boron carbide and graphite,or a material of low atomic number. Other materials, however, may beused in place of, or in addition to, these example materials. In otherimplementations of the energy degrader that include polyhedra such aswedges, tetrahedra, or toroidal polyhedral, or curved three-dimensionalstructures, such as cylinders, spheres, or cones, these structures maybe made of one or more of the following example materials: polycarbonatesuch as LEXAN™, carbon, beryllium, boron carbide, a composite materialcomprised of boron carbide and graphite, or a material of low atomicnumber.

In some implementations, structures of the range modulator containingboron carbide may include only boron carbide; that is, the structuresmay be pure boron carbide. In some implementations, structurescontaining boron carbide may include boron carbide in combination withanother material, such as graphite, polycarbonate, carbon, or beryllium.In some implementations, every structure—for example, plate, polyhedron,or curved three-dimensional structure—in the energy degrader may containall or part boron carbide. In some implementations, differentstructures—for example, plates, polyhedra, or curved three-dimensionalstructures—in the energy degrader may include different materials. Forexample, one or more plates in the energy degrader may be made of pureboron carbide and one or more other plates of the same energy degradermay be made of or include one or more of polycarbonate, carbon, and/orberyllium. Other materials may also be used. For example, one or moreplates or portions thereof in the energy degrader may be made of acomposite material comprised of boron carbide and graphite.

One or more of the plates is movable into, or out of, the beam path tothereby change the energy of the particle beam and, thus, the depth atwhich most of the dosage of the particle beam is deposited within theirradiation target. Plates are moved physically into and out of the pathof the particle beam. For example, as shown in FIG. 9 , a plate 470moves along the direction of arrow 472 between positions in the path ofthe particle beam 473 and outside the path of the particle beam. Theplates are computer-controlled. Generally, the number of plates that aremoved into the path of the particle beam corresponds to the depth atwhich scanning of an irradiation target is to take place. Thus, dosagefrom the particle beam can be directed into the interior of a target byappropriate control of one or more plates.

In some implementations, individual plates of range modulator 460 areeach coupled to, and driven by, a corresponding motor 464. In general, amotor includes a device that converts some form of energy into motion. Amotor may be rotary or linear, and may be electric, hydraulic, orpneumatic. For example, each motor may be an electrical motor thatdrives a lead screw to extend a plate into the beam field or to retracta plate out of the beam field, including to cause motion of the plate totrack or to trail motion of the particle beam within the beam field. Forexample, each motor may be a rotary motor that drives a correspondinglinear actuator to control movement of a corresponding structure. Insome implementations, individual plates of range modulator 460 are eachcoupled to, and driven by, a corresponding actuator. In some examples,actuators include mechanical or electro-mechanical devices that providecontrolled movements and that can be operated electrically by motors,hydraulically, pneumatically, mechanically, or thermally. In someexamples, an actuator includes any type of motor that is operated by asource of energy, such as electric current, hydraulic fluid pressure, orpneumatic pressure, and that converts that energy into motion.

In some implementations, an energy degrader containing boron carbidestructures (or structures comprised of other material) may be located inthe treatment room where the particle beam is applied to the patient.For example, the energy degrader may be located between the scanningmagnet and the patient. In an example, the energy degrader may belocated in a nozzle on a system's inner gantry, examples of which aredescribed with respect to FIGS. 26, 27, and 28 .

The energy degrader may be located close to the patient so as to limitthe amount that the particle beam is scattered or dispersed followingpassage through one or more plates or other structures. In someimplementations, the energy degrader may be located no more than fourmeters from the patient along a beam line of the particle beam. In someimplementations, the energy degrader may be located no more than threemeters from the patient along a beamline of the particle beam. In someimplementations, the energy degrader may be located no more than twometers from the patient along a beam line of the particle beam. In someimplementations, the energy degrader may be located no more than onemeter from the patient along a beamline of the particle beam. In someimplementations, the energy degrader may be located no more thanone-half a meter from the patient along a beamline of the particle beam.In some implementations, the energy degrader may be located within thenozzle no more than four meters from the patient along a beamline of theparticle beam. In some implementations, the energy degrader may belocated within the nozzle no more than three meters from the patientalong a beam line of the particle beam. In some implementations, theenergy degrader may be located within the nozzle no more than two metersfrom the patient along a beamline of the particle beam. In someimplementations, the energy degrader may be located within the nozzle nomore than one meter from the patient along a beamline of the particlebeam. In some implementations, the energy degrader may be located withinthe nozzle no more than one-half a meter from the patient along a beamline of the particle beam.

In general, boron carbide may be cheaper and safer to use than someother materials that may be used to degrade the energy of the particlebeam, such as beryllium. In general, boron carbide has a relatively lowatomic weight and a high density and may compare favorably in itsscattering properties to some other materials that may be used todegrade the energy of the particle beam, such as carbon (e.g., graphite)and polycarbonate. Reducing the beam scattering results in a reducedbeam spot size; that is, the cross-sectional size of the beam. A reducedspot size provides for improved conformality in a pencil beam scanningsystem and higher localized dose rate. In other words, reducing the spotsize reduces the area over which dose is deposited. As a result, theconcentration of protons deposited within a single spot increases,thereby increasing the dose rate within the area of the single spot.Increasing the dose rate within the area of the single spot is desirablewhen performing scanning using ultra-high (or FLASH) dose rates since itfacilitates deposition of an ultra-high dose of protons within aprescribed period. Examples of periods during which ultra-high doses areapplied are described herein.

FIG. 29 is a graph showing the change in particle beam spot size fordifferent particle beam energies for different materials used in theenergy degrader to change the energy of the particle beam. In thisexample, LEXAN™, carbon (e.g., graphite), boron carbide, and berylliumare shown. According to the graph of FIG. 29 , for example, a boroncarbide degrader structure produces a particle beam having a spot sizeof less than 1.2 centimeters (cm) sigma at an energy of 70 MeV (Millionelectron Volts). In this example, the spot size is measured at theoutput of the degrader structure. The spot may scatter the farther thebeam travels through the air, which will cause an increase in spot size.However, placing the degrader sufficiently close to the patient willlimit scattering. In addition, in some but not all cases, a configurablecollimator may be placed between the energy degrader and the patient tocollimate the particle beam.

In addition to the foregoing advantages, a boron carbide based energydegrader may be reduced in size relative to energy degraders that usepolycarbonate, for example. That is, a boron carbide based energydegrader may achieve substantially the same effect as a polycarbonatebased energy degrader, but the boron carbide based energy degrader mayhave a smaller form factor than the polycarbonate based energy degrader.This is because the density of boron carbide is greater than thedensities of polycarbonate. In some examples, an energy degradercomprised of pure boron carbide plates may be 30 centimeters (cm) to 40cm thick along the beam line. The plates may have the same or varyingthicknesses. The thickness of the plates and of the energy degraderitself will depend upon various factors such as the overall amount ofenergy change required and the number of layers to be treated, which maydetermine the number and thickness of each of the plates.

The reduced size of an energy degrader comprised of boron carbide makesthe energy degrader less obtrusive in the treatment room. For example,an energy degrader comprised of all or some boron carbide structures maybe housed within the nozzle on the inner gantry. The nozzle, includingthe energy degrader may be retracted fully within the inner gantry,thereby taking the energy degrader out of the way of a technicianadministering the treatment. In some implementations, the inner gantrymay be flush with a wall of the treatment room, in which case retractingthe nozzle and the energy degrader fully within the inner gantry causesthe nozzle and energy degrader to retract fully within the wall.

FIG. 10 shows an example implementation of a range modulator such as aboron carbide based range modulator that uses linear motors to controloperations of energy-absorbing plates 101, 102, and 103. The rangemodulator of FIG. 10 may otherwise have the configuration of the rangemodulator of FIG. 8 . Although only three plates are shown in theexample of FIG. 10 , any appropriate number of plates may be included,as illustrated by ellipses 106.

Taking plate 102 as an example, an example linear motor that controlsoperation of plate 102 includes a movable component and stationarycomponent comprised of two parts—in this example, magnets 110 a and 110b. The two magnets are arranged side-by-side, with their poles aligned.That is, as shown, the positive pole (+) of magnet 110 a is aligned tothe positive pole (+) of magnet 110 b, and the negative pole (−) ofmagnet 110 a is aligned to the negative pole (−) of magnet 110 b. Themovable component includes a coil-carrying plate 109 between magnets 110a and 110 b. Coil-carrying plate 109 is connected physically toenergy-absorbing plate 102 and controls movement of energy-absorbingplate 102 along the directions of arrow 111, e.g., into and out of thepath of the particle beam.

As explained, coil-carrying plate 109 includes one or more conductivetraces or other conductive structures that pass current in order togenerate a magnetic field. The magnetic field is controlled bycontrolling the current through the coil-carrying plate in order tocontrol movement of the coil-carrying plate, and thus ofenergy-absorbing plate 102. That is, current through the coils generatesa magnetic field that interacts with the magnetic field produced bymagnets 110 a and 110 b. This interaction causes movement ofcoil-carrying plate 109 and of energy-absorbing plate 102 along thedirection of arrow 111, either into, or out of, the particle beam path.For example, larger magnetic fields generated by the coil-carrying plate109 may cause the energy-absorbing plate to move into the particle beampath and smaller or opposite magnetic fields generated by thecoil-carrying plate may cause the energy-absorbing plate to retract awayfrom the particle beam path.

In some implementations, the conductive traces or other conductivestructures on the coil-carrying plate may include three windingsembedded in aluminum. In some implementations, the energy-absorbingplate may be physically attached to the coil-carrying plate and movewith the coil-carrying plate. In some implementations, the number ofwindings and the materials used may be different than those describedherein. In some implementations, the coil-carrying plate may be anintegral part of the energy-absorbing plate. For example, theenergy-absorbing plate itself may include the conductive structures ortraces.

As shown in FIG. 10 , in some implementations, the current through thecoil-carrying plates may be controlled by signals received from acontrol system, such as computing system 114. The computing system maybe susceptible to neutron radiation and, therefore, may be located in aremote room 116. In some implementations, remote room 116 may beshielded from neutron radiation produced by the particle accelerator. Insome implementations, the remote room may be located far enough awayfrom the treatment room 117 so as not to be affected by neutronradiation from the particle accelerator. In some implementations, thecomputing system may be located in the treatment room, but may beshielded from neutron radiation emitted by the particle accelerator. Insome implementations, all computing functionality is shielded fromneutron radiation and the electronics that are not shielded can stilloperate in the presence of neutron radiation. Encoders are examples ofsuch electronics.

In this regard, encoders (not shown) may include or more of lasersensors, optic sensors, or diode sensors. The encoders detect movementof the coil-carrying plates, e.g., by detecting where markings or otherindicia on the coil-carrying plates or on structures connected to, andthat move with, the coil-carrying plates are located relative to theencoders. This information about where the coil-carrying plates are isfed back to the computing system and is used by the computing system toconfirm the position of the coil-carrying plates during operation. Theencoders may be located at any appropriate location. In someimplementations, the encoders are located on a housing that includes thecoil-carrying plates. As the plates move, markings or other indicia thatmove with the coil-carrying plates move past the encoders. The encodersthen relay that information to computing system 114. Computing system114 may use that information to control operation of the rangemodulator, including positioning its energy-absorbing plates.

Computing system 114, which may be comprised of one or more processingdevices, may be programmed to control the proton therapy system todeliver proton therapy based on a treatment plan, including componentsof the scanning system to implement ultra-high dose rate radiationtreatment column-by-column in an irradiation target, such as a volume ina patient containing diseased tissue. For example, the computing systemmay be controllable based on the treatment plan to output one or morecontrol signals to control one or more of the linear motors to extend orto retract one or more of the energy-absorbing plates during scanning.For example, the computing system may be controllable based on thetreatment plan to output one or more control signals to control one ormore electrical motors to extend or to retract one or more of theenergy-absorbing plates during scanning. The computing system mayinclude one or more processing devices, such as microprocessors,microcontrollers, field-programmable gate arrays (FPGAs), orapplications-specific circuits (ASICs), for example.

FIG. 30 shows components of an example treatment planning system 1200that may be implemented on the control system, such as computing system114, or that may be implemented on a different computing system that isseparate from the control system. The treatment planning system includesmodules—which may include, for example, data and/or routines comprisedof source code, compiled code, or interpreted code—to implementdifferent functions of the treatment planning system. The modules may betime-dependent in the sense that delivery of radiation at an ultra-highdose rate is dependent upon the ability to deliver that radiation at aspecific dose in a specific time. Examples of doses and times areprovided herein.

An example module includes a prediction model 1201. The prediction modelcharacterizes or models the particle therapy system including, but notlimited to, a particle accelerator that generates radiation for deliveryto a patient and the scanning system used to direct the radiation. Theprediction model also characterizes or models the patient to be treated,including volumes where radiation is to be delivered and volumes whereradiation is not to be delivered. In some implementations, theprediction model may be implemented at least in part using one or moredata structures stored in computer memory. An example data structureincludes a collection of data values, the relationships among thosevalues, and functions or operations that can be applied to the data.Examples of data structures that may be used to implement the predictionmodel may include one or more of the following: lookup tables (LUTs),arrays, stacks, queues, linked lists, trees, graphs, tries or prefixtrees, or hash tables. The prediction model may also include executablecode to interact with other modules and to retrieve data from a datastructure. The prediction model may also be implemented using one ormore computer programming objects written in an object-orientedlanguage.

Prediction model 1201 may be populated manually, automatically, or acombination of manually and automatically. For example, to populate theprediction model manually, code to implement part of the predictionmodel may be executed to generate prompts that are displayed to atreatment planning technician on an electronic display device. Atreatment planning technician may enter information into the predictionmodel in response to the prompts. The information may include valuesthat are based on, or that are assigned to, physical properties of theparticle therapy system, the patient, the target in the patient, andother relevant parameters. The information may relate to thecapabilities of the particle therapy system to deliver radiation to apatient time-sequentially; for example, in a sequence of spots orcolumns over a time required to deliver a FLASH dose or radiation. Forexample, the information may relate to, but is not limited to, astructure of pulses of a particle beam produced by the particleaccelerator—for example the duration of each pulse, a maximum dose perpulse of the particle beam—for example a number of particles per pulse,a sweep time of a scanning magnet to move the particle beam a specifieddistance, a time it takes to change an energy of the particle beam—forexample by changing the energy of a variable-energy accelerator, a timeit takes to move one or more energy-absorbing structures to change theenergy of the particle beam, a strategy for regulating the doses—forexample, to apply ultra-high dose rate radiation in columns of a targetor to apply dose at lower rates layer-by-layer in a target, a time ittakes to move a collimator for collimating the particle beam, a time ittakes to configure the collimator, and/or a time it takes to control arange modulator to change a Bragg peak of particles in the particlebeam. Thus, in general, the prediction model may characterize the timingat which radiation—for example, particle therapy—is or can be deliveredto the patient. The information may include the type of disease—forexample, tumor—to be treated, the location of the tumor in the patient'sbody specified in XYZ coordinates for example, the size and shape of thediseased tissue including its volume, the type of healthy tissuesurrounding the diseased tissue, the location of the healthy tissuespecified in XYZ coordinates for example, the size and shape of thehealthy tissue including its volume, and any other information about thepatient and the disease that may be pertinent to treatment such as pastmedical history, prior treatment, surgery, and the like.

In some implementations, all or some of the foregoing information in theprediction model may be stored in the control system, such as computingsystem 114. The treatment planning system may query the control systemto obtain all or some of this information absent input from a user.

An example module includes a RBE model 1202. As explained previously,the RBE model characterizes the relative biological effectiveness ofradiation on tissue in a time-dependent manner. For example, whenradiation is applied at ultra-high (FLASH) dose rates, healthy tissueexperiences less damage than when that same tissue is irradiated withthe same dose over a longer time scale, while tumors are treated withsimilar effectiveness. The RBE model may include information aboutdifferent types of healthy and non-healthy tissues and the effectsdifferent dose rates of radiation have on those different types oftissues. For example, the RBE model may specify the doses of radiationnecessary to treat adenomas, carcinomas, sarcomas, or lymphomaseffectively. The doses needed to treat such tumors are not necessarilytime-dependent; accordingly dose rates may not be specified. However, insome implementations, dose rates for treating tumors may be specified inthe RBE model. For reasons explained previously, the rate at which doseis applied to healthy tissue during radiation treatment can affect thedamage that the radiation causes to the healthy tissue. Accordingly, theRBE model may specify time-dependent effects of dose rates on healthytissue. In this regard, examples of non-healthy tissue include benignand malignant neoplasms and bodily tissue affected by other types ofdiseases. Examples of healthy tissue include bones, skin, muscle, ororgans that are not affected by disease. The RBE model may also includethe effects that different types or radiation have on different types oftissues at different dose rates. The example systems described hereinuse proton radiation; however, the RBE model may include informationabout other types of radiation such as other types of ion radiation,photon radiation, or X-ray radiation.

The RBE model may also include information about how different types ofhealthy and non-healthy tissues affect radiation applied to thosetissues. As explained previously, an equivalent dose may include anamount of radiation deposited that is needed to treat diseased tissue inthe patient accounting for biological effects of tissue in the patienton the radiation deposited. In this regard, some tissue may not absorball of the dose of radiation deposited. Accordingly, the dose may beweighted using information from the RBE model to account for thebiological effects of tissue on the radiation. The resulting equivalentdose takes biological effects on radiation into account. For example,given tissue may degrade the destructive effect of a certain type ofradiation by 10%. Accordingly, the equivalent dose may be increased by10% to account for this biological factor.

In some implementations, the RBE model may be implemented at least inpart using one or more data structures stored in computer memory. Anexample data structure includes a collection of data values, therelationships among those values, and functions or operations that canbe applied to the data. Examples of data structures that may be used toimplement the RBE model may include one or more of the following: lookuptables (LUTs), arrays, stacks, queues, linked lists, trees, graphs,tries or prefix trees, or hash tables. The RBE model may also includeexecutable code to interact with other modules and to retrieve data froma data structure. The RBE model may also be implemented using one ormore computer programming objects written in an object-orientedlanguage.

RBE model 1202 may be populated manually, automatically, or acombination of manually and automatically. For example, to populate theRBE model manually, code to implement part of the RBE model may beexecuted to generate prompts that are displayed to a treatment planningtechnician on an electronic display device. A treatment planningtechnician may enter information into the RBE model in response to theprompts. The information may include values that are based on, or thatare assigned to, different types of tumors, different types ofradiation, different doses, and different dose rates. For example, theRBE model may include one or more lists of disease, such as tumors. TheRBE model may identify different types of radiation, such as proton,photon, or X-ray, that can treat each disease. The RBE model mayidentify, for each type of radiation, one or more ranges of doses thatcan treat a given volume of disease. The RBE model may identify, foreach type of radiation, one or more ranges of dose rates that can treata given volume of disease. In this regard, as noted, dose rate may notalways be a factor in treating diseased tissue; the dose itself may becritical in some cases irrespective of dose rate. The RBE model mayidentify different types of healthy tissue, such as muscle, bone, skin,and organs. The RBE may specify the effect that different dose rates—forexample, dose applied over a period of time—of different types ofradiation have on those types of tissue. For example, the RBE mayspecify the effects of different levels of FLASH and non-FLASH doserates for different types of radiation on different types of tissue. Forexample, the RBE may specify the effects of different levels of FLASHand non-FLASH dose rates for proton radiation on healthy muscle, bone,skin, and organs. The effects may be quantified. For example, damage totissue may be specified on a numerical scale of 0 to 10, with 0 being nodamage and 10 being destruction of the tissue. For example, the effectsmay be specified using descriptive information that can be read andunderstood electronically, for example, by the dose calculation engine.The RBE model may specify the effects of different types of radiation onthat radiation's effectiveness and include weighting factors tocounteract these effects.

In some implementations, all or some of the foregoing information in theRBE model may be stored in the control system, such as computing system114. The treatment planning system may query the control system toobtain all or some of this information absent input from a user such asa treatment planning technician.

An example module includes dose calculation engine 1203. Dosecalculation engine 1203 is configured—for example, written orprogrammed—to determine doses of radiation to deliver to voxels in thepatient and, in some examples, the rates at which those doses are to bedelivered to the patient. In this regard, dose calculation engine 1203may receive, from a treatment planning technician for example, a totaltarget radiation dose to deliver to diseased tissue in the patient, thedose distribution across the tissue, or both the total target dose andthe dose distribution. The dose calculation engine obtains informationabout the system delivering the radiation and the patient from theprediction model. The dose calculation engine obtains information aboutthe RBE of the radiation to be delivered by the system to the diseasedtissue and the healthy tissue from the RBE model. The information fromthe prediction model and the RBE model is then used to determine dosesand dose rates of radiation to be applied to the patient.

For example, the dose calculation engine obtains the composition of atumor to be treated in the patient. As noted, this information may beobtained, for example, from the prediction model or from input by atreatment planning technician. The composition may include the type ofthe tumor, the size or volume of the tumor, and the shape of the tumor.The dose calculation engine obtains information about healthy tissue inthe patient adjacent to the tumor. This information may be obtained, forexample, from the prediction model or from input by a treatment planningtechnician. The information may include the type of healthy tissue, thelocation of the healthy tissue relative to the diseased tissue, andwhether the healthy tissue has previously been exposed to radiation. Thedose calculation engine also obtains information about the maximum doserates that can be achieved using the particle accelerator, the scanningsystem, and other hardware in the particle therapy system. Thisinformation may be obtained from the prediction model or determinedbased on information in the model. The dose calculation engine alsoobtains information about how doses of the radiation applied by thesystem treat, effect, or both treat and effect the diseased tissue andthe healthy tissue. This information may be obtained from the RBE model.The dose calculation engine also obtains information about how tissuewithin the patient affects radiation applied by the system (for example,radiation absorption) and any weighting factors needed to counteractsuch effects. This information may be obtained from the RBE model.

The dose calculation engine is configured to determine the dose regimento be applied to the patient. The dose regimen may include equivalentdoses to be delivered to the patient and the rates at which thoseequivalent doses are to be delivered based on the foregoing informationobtained from the prediction model and the foregoing informationobtained from the RBE model. For example, as explained previously, whenradiation is applied at ultra-high (FLASH) dose rates, healthy tissueexperiences less damage than when that same tissue is irradiated withthe same dose over a longer time scale, while tumors are treated withsimilar effectiveness. In other words, for tumors or other diseasedtissue, a critical factor for treatment is total radiation dose asopposed to dose rate, whereas for healthy tissue, dose rate is a factorin reducing damage where none is desired. In this example, knowing thecharacteristics of the diseased tissue to be treated in the patient, thecharacteristics of the healthy tissue adjacent to the diseased tissue,the capabilities of the system delivering the radiation, the RBE of theradiation on the diseased tissue and the healthy tissue, the target doseand/or dose distribution to be applied, the dose calculation enginebreaks the disease tissue—for example, a target volume—to be treatedinto voxels, determines the dose of radiation to be applied to eachvoxel, and sets the rate at which that dose is to be delivered. Forexample, the dose calculation engine may determine to apply to eachvoxel a dose of radiation that exceeds one (1) Gray-per-second for aduration of less than five (5) seconds. For example, the dosecalculation engine may determine to apply to each voxel a dose ofradiation that exceeds one (1) Gray-per-second for a duration of lessthan 500 ms. For example, the dose calculation engine may determine toapply to each voxel a dose of radiation that is between 40Gray-per-second and 120 Gray-per-second for a duration of less than 500ms. The radiation may be applied column-by-column as described, forexample, with respect to FIG. 12 to 19 or 33 to 42 , thereby reducingdamage to healthy tissue through which the radiation travels to reachthe target. In some implementations, ultra-high dose rate radiation maybe applied to the entire target at once, for example, by scattering theradiation across the target, changing the energy as described withrespect to FIG. 12 to 19 or 33 to 42 while the radiation is stationary,and using a bolus to limit exposure of healthy tissue to the radiation.

In some implementations, the dose calculation engine may look at a timescale over which dose is to be delivered and apply one or more weightsto individual doses in an attempt to adjust the RBE of the radiation.For example, the dose calculation engine may be configured to apply aweighting factor to a dose to a voxel to adjust the RBE based on aduration over which the dose is to be applied. As noted, biology mayaffect how doses of radiation are deposited and how tissues react to thedoses. Weighting factors may be applied to counteract these biologicaleffects. The weighting factors produce an equivalent dose which, asexplained previously, has been adjusted to account for the biologicaleffects in order to deliver an amount of destructive radiation that canactually be absorbed by the patient. In an example, a weighting factorcauses the dose to increase for a duration to produce an ultra-high doserate or to increase an already ultra-high dose rate. In an example, aweighting factor causes a dose to decrease for a duration while stillbeing an ultra-high dose rate or to decrease to a conventional doserate.

An example module includes sequencer 1204 (or “optimizer”). Sequencer1204 generates instructions for sequencing delivery of the doses basedon the model. In some implementations, the sequencer is configured togenerate instructions for sequencing delivery of doses in order tooptimize the effective doses determined by the dose calculation engine.For example, the instructions may be executable by the control system tocontrol the particle therapy system to provide the dosage specified toeach voxel at the dose rate specified. Delivery of the dosage may beautomatic or it may require input from a user. As previously explained,the sequencer is configured—for example, written or programmed—tosequence delivery of the doses based on information from the predictionmodel or other information provided, for example, by a technician. Thesequence of doses may be intended to optimize—for example, tominimize—the time it takes to deliver doses and, therefore, may promotedelivery of radiation at ultra-high dose rates. For example, thesequencer may be configured to sequence delivery of the doses based onone or more of the following, two or more of the following, three ormore of the following, four or more of the following, five or more ofthe following, or all of the following: a structure of pulses of aparticle beam produced by the particle accelerator, a maximum dose perpulse of the particle beam, a sweep time of a scanning magnet to movethe particle beam, a time it takes to change an energy of the particlebeam, a time it takes to move one or more energy-absorbing structures tochange the energy of the particle beam, a strategy for regulating thedoses, a time it takes to move a collimator for collimating the particlebeam, a time it takes to configure the collimator, or a time it takes tocontrol a range modulator to change a Bragg peak of particles in theparticle beam. In this regard, operations such as these affect the timesat which dose may be delivered. To achieve ultra-high dose rates, timingis a consideration as described herein. Accordingly, factors such asthese are taken into account when determining where dose is to bedelivered to an irradiation target in order to meet the time constraintsnecessary to achieve ultra-high dose rates and benefits thereof.

In some implementations, values may be determined for, or assigned to,all or some of the following: a structure of pulses of a particle beamproduced by the particle accelerator, a maximum dose per pulse of theparticle beam, a sweep time of a scanning magnet to move the particlebeam, a time it takes to change an energy of the particle beam, a timeit takes to move one or more energy-absorbing structures to change theenergy of the particle beam, a strategy for regulating the doses, a timeit takes to move a collimator for collimating the particle beam, a timeit takes to configure the collimator, and a time it takes to control arange modulator to change a Bragg peak of particles in the particlebeam.

The sequencer knows how dose is to be delivered—for example, in columnsor spots and at an ultra-high dose rate—and determines the order inwhich to deliver doses based on calculations performed that take theforegoing values into account. For example, referring to FIG. 31 ,overlapping voxels of a target are shown, including adjacent voxels1205, 1206, 1207, and 1208. The sequencer may determine, based on itscalculations, that it is possible to move a particle beam from voxel1205 to voxel 1206 and still achieve ultra-high dose rates for allvoxels in the target since the particle beam can then be moved toadjacent voxel 1207, to adjacent voxel 1208, and so forth. The sequencermay also determine, based on its calculations, that it is not possibleto move the particle beam from voxel 1205 to voxel 1207 and stillachieve ultra-high dose rates for all voxels in the target. This may bebecause it would take too much time to move or to reconfigure hardwarein the system, such as the collimator or energy-absorbing plates, whenthe beam moves between non-adjacent voxels 1206 and 1208 withoutinterrupting the particle beam. In other words, the sequencer hasdetermined a treatment sequence that treats adjacent voxels in sequenceat ultra-high dose rates, thereby reducing the amount of mechanicalmovements to reconfigure the system between treatment locations whilemaintaining the particle beam.

In some implementations, the sequencer may assign several differentvalues to each of the following: a structure of pulses of a particlebeam produced by the particle accelerator, a maximum dose per pulse ofthe particle beam, a sweep time of a scanning magnet to move theparticle beam, a time it takes to change an energy of the particle beam,a time it takes to move one or more energy-absorbing structures tochange the energy of the particle beam, a strategy for regulating thedoses, a time it takes to move a collimator for collimating the particlebeam, a time it takes to configure the collimator, a time it takes tocontrol a range modulator to change a Bragg peak of particles in theparticle beam. The sequencer may perform calculations that iteratethrough these different values to obtain an optimized sequence at whichdoses of radiation should be applied to meet a desired dose rate.Optimization may include obtaining the best sequence in terms of timeand treatment or obtaining an improved sequence in terms of time andtreatment.

By way of example, a cubic treatment volume, such as a tumor,approximately 4 cm×4 cm×4 cm is to be treated to 2 Gy. The treatmentplan includes of 5 layers each having 25 spots; that is, 5 rows×5columns for 125 total spots in the volume. The system delivers one pulseof protons every 1.3 ms. In this example, each spot must receive atleast 4 pulses so the dose to that spot can be delivered accuratelythrough active dose control of the charge in each pulse. The deepestlayer requires 6 pulses because more charge is required there. Thescanning magnet moves fast enough that it can move from one spot to anadjacent spot in less than 1.3 ms, so no additional time is required forbeam scanning. Energy layer switching takes 50 ms in this example.

The following example treatment plan excerpt is implemented usinglayer-by-layer treatment such as that described with respect to FIG. 1 .If the treatment is arranged in layers from deepest layer (1) toshallowest layer (5):

-   -   Beam delivery begins at time t=0    -   Each spot in layer 1 takes 1.3 ms×6 pulses=7.8 ms to deliver    -   No time to move from spot to spot    -   Entire layer takes 7.8 ms×25 spots=195 ms.    -   50 ms to switch to next layer, beam delivery on next layer        begins at t=245 ms.    -   Each spot in layers 2 to 5 takes 4 pulses×1.3 ms=5.2 ms to        deliver. Each layer takes 5.2 ms×25 spots=130 ms.    -   Layer 2 beam delivery ends at t=325 ms.    -   Layer 3 beam delivery ends at t=505 ms.    -   Layer 4 beam delivery ends at t=685 ms.    -   Layer 5 beam delivery ends, total treatment ends at t=865 ms.        In the above example, 2 Gy was delivered to the entire volume in        865 ms for an average dose rate of 2.3 Gy/s, which is well below        an example “FLASH” dose such as 40 Gy/s under some definitions.        But, each spot in the deepest layer reached 2 Gy in about 7.8        ms, neglecting the dose that spills over into adjacent spots        from each pulse. That is a dose rate of 256 Gy/s for those        spots. As dose is delivered to the deepest layer, dose is also        delivered to the shallower layers. So. each spot in the        shallowest layer received dose over almost the entire 865 m/s        and, as a result, experiences a lower dose rate than 256 Gy/s.

The following example treatment plan excerpt is implemented usingcolumn-by-column treatment such as that described with respect to FIG. 2. If the same amount of treatment described in the preceding paragraphwere to be rearranged into 25 columns instead of 5 layers, with eachcolumn being 5 spots deep:

-   -   Beam delivery begins at t=0    -   The spot in layer 1 takes 7.8 ms to deliver    -   50 ms to switch to the next shallower depth    -   Layer 2 spot beam delivery begins at 57.8 ms    -   Layer 3 spot beam delivery begins at 113 ms    -   Layer 4 spot beam delivery begins at 168.2 ms    -   This column completes at 223.4 ms    -   Treatment completes at 223.4 ms×25 columns=5.6 s.        This treatment results in a longer treatment time overall, but        each column experiences a dose rate of 2 Gy/223.4 ms=9 Gy/s.        This a higher dose rate, but may not be a FLASH dose rate under        some definitions for every part of every column. But, assume an        increase in the maximum proton charge per pulse so that with the        same number of pulses it is possible to reach 10 Gy instead of 2        Gy. In this case, the dose rate for the layer-by-layer treatment        examples goes up to 11.5 Gy/s. In this case, every voxel in the        column-by-column treatment example is delivered dose at a rate        of 45 Gy/s. Also, the layer switching time is decreased from 50        ms to 25 ms. In this example, each column in the column delivery        takes 123.4 ms instead of 223.4 ms. In this example, the        columnar dose rates for the lower maximum pulse charge is 16.3        Gy/s, while the columnar dose rates for the high maximum pulse        charge is 81.5 Gy/s for every voxel in the treatment volume. A        dose rate of 81.5 Gy/s for 123.4 ms qualifies as a FLASH dose        rate under most definitions of FLASH.

Referring to FIG. 11 , the control system may be configured—for example,programmed—to implement the treatment plan for a target, such as tumorin the patient. As explained previously, the treatment plan may specifyparameters including the dose of particle beam (for example, equivalentdoses) to deliver and the rates (for example, an ultra-high dose rate ora standard dose rate) at which doses should be delivered to voxels in apatient. The treatment plan may also specify the locations at whichdosed are to be delivered to the target and sequences at which parts ofthe target are to be treated. For example, referring to FIGS. 1 and 2 ,the parts of the target may be columns or layers as described herein.Initially, the control system may control a particle accelerator—in thisexample, synchrocyclotron 310—to generate (1101) a particle beam havingspecified parameters, including beam current and intensity. In someimplementations, the beam current of the particle beam is 100nanoamperes (nA) of current or less. In some implementations, the beamcurrent of the particle beam is 50 nA of current or less. Levels of beamcurrent on the order of nanoamperes may reduce risks of injury to thepatient, may reduce risks of damage to the accelerator or otherelectronics in the treatment room, or may reduce risks of both suchinjury and damage.

The intensity of the particle beam may also be controlled (1102), ormodulated, to control or to change the dose applied to the target atdifferent particle beam energies. Thus, intensity-modulated protontherapy (IMPT) may be delivered using the techniques described herein.In some implementations, the same irradiation target may be treatedusing beams having different or the same intensities from multipledifferent angles either at FLASH dose rates or at dose rates lower thanFLASH dose rates. For example, an irradiation target may be treated atFLASH or non-FLASH dose rates by delivering radiation by columns atdifferent angles. In such examples, because the radiation is deliveredat different angles, healthy tissue that is not being treated may besubjected to radiation only once.

The beam intensity is based, at least in part, on the number ofparticles in the particle beam. For example, the beam intensity may bedefined by the number of particles in the particle beam. The intensityof the particle beam may change from spot to spot of the particle beam.Additionally, the intensity of one spot of the particle beam may beindependent of the intensity of one or more other spots of the particlebeam, including immediately adjacent spots. Accordingly, in someexamples, any spot in a three-dimensional volume may be treated to anarbitrary dose independent of the dose to one or more adjacent spots.The control system may control particle beam intensity using one or moretechniques.

In an example technique, the intensity of the particle beam can becontrolled by varying the time duration of the pulses of particlesobtained from the plasma column. In more detail, the RF voltage sweepsfrom a starting (e.g., maximum) frequency (e.g., 135 megahertz (MHz)) toan ending (e.g., minimum) frequency (e.g., 90 MHz). The particle sourceis activated for a period of time during the RF sweep to produce aplasma column. For example, in some implementations, the particle sourceis activated at 132 MHz for a period of time. During that time,particles are extracted from the plasma column by the electric fieldproduced by the RF voltage. The particles accelerate outwardly inexpanding orbits as the RF voltage frequency drops, keeping pace withthe decreasing magnetic field and increasing relativistic mass until theparticles are swept out at a time (e.g., about 600 microseconds) later.Changing the duration for which the particle source is activated changesthe width of the pulse of particles that are extracted from the plasmacolumn during a frequency sweep. Increasing the pulse width causes anincrease in the amount of particles extracted and thus an increase inthe intensity of the particle beam. Conversely, decreasing the pulsewidth causes a decrease in the amount of particles extracted and thus adecrease in the intensity of the particle beam.

In another example technique, the intensity of the particle beam can becontrolled by changing a voltage applied to cathodes in the particlesource. In this regard, the plasma column is generated by applying avoltage to two cathodes of the particle source and by outputting a gas,such as hydrogen (H₂), in the vicinity of the cathodes. The voltageapplied to the cathodes ionizes the hydrogen and the background magneticfield collimates the ionized hydrogen to thereby produce the plasmacolumn. Increasing the cathode voltage causes an increase in the amountof ions in the plasma column and decreasing the cathode voltage causes adecrease in the amount of ions in the plasma column. When more ions arepresent in the plasma column, more ions can be extracted during the RFvoltage sweep, thereby increasing the intensity of the particle beam.When fewer ions are present in the plasma column, fewer ions can beextracted during the RF voltage sweep, thereby decreasing the intensityof the particle beam.

In another example technique, the intensity of the particle beam can becontrolled by varying the amount of hydrogen supplied to the particlesource. For example, increasing the amount of hydrogen supplied to theparticle source results in more opportunity for ionization in the plasmacolumn in response to the cathode voltage. Conversely, decreasing theamount of hydrogen supplied to the particle source results in lessopportunity for ionization in the plasma column in response to thecathode voltage. As noted above, when more particles are present in theplasma column, more particles are extracted during the RF voltage sweep,thereby increasing the intensity of the particle beam. When fewerparticles are present in the plasma column, fewer particles areextracted during the RF voltage sweep, thereby decreasing the intensityof the particle beam.

In another example technique, the intensity of the particle beam can becontrolled by varying the magnitude of the RF voltage used to extractparticles from the plasma column. For example, increasing the magnitudeof the RF voltage causes more particles to be extracted from the plasmacolumn. Conversely, decreasing the magnitude of the RF voltage causesfewer particles to be extracted from the plasma column. When moreparticles are extracted, the particle beam has a greater intensity thanwhen fewer particles are extracted.

In another example technique, the intensity of the particle beam can becontrolled by varying the starting time during the frequency sweep atwhich the particle source is activated and, thus, during which particlesare extracted. More specifically, there is a finite window during thefrequency sweep during which particles can be extracted from the plasmacolumn. In an example implementation, the frequency sweeps from about135 MHz to about 90 MHz at a substantially constant rate. In thisexample, particles can be extracted at about the beginning of thedownward slope between starting and ending frequencies, e.g., between132 MHz and 131 MHz respectively, and the particle source can beactivated for a period of time, e.g., for about 0.1 microseconds (μs) to100 μs (e.g., 1 μs to 10 μs or 1 μs to 40 μs). Changing the frequency atwhich the particle source is activated affects the amount of particlesthat are extracted from the particle beam and therefore the intensity ofthe particle beam.

In another example technique, pulse blanking may be used to control theintensity of the particle beam. In this regard, the RF frequency sweepis repeated a number of times per second (e.g., 500 times/second). Theparticle source could be activated for each frequency sweep (e.g., every2 ms). Pulse blanking reduces the number of particles extracted from theparticle beam by not activating the particle source during everyfrequency sweep. To achieve maximum beam intensity, the particle sourcemay be activated every frequency sweep. To reduce beam intensity, theparticle source may be activated less frequently, e.g., every second,third, hundredth, etc. sweep.

In another example technique, the intensity of the particle beam can becontrolled by applying a DC bias voltage to one or more dees used toapply the RF voltage to the particle accelerator cavity. In this regard,the particle accelerator includes an active dee plate that is a hollowmetal structure having two semicircular surfaces that enclose a space inwhich the protons are accelerated during their rotation around thecavity enclosed by the magnet yokes. The active dee is driven by an RFsignal that is applied at the end of an RF transmission line to impartan electric field into the space. The RF field is made to vary in timeas the accelerated particle beam increases in distance from thegeometric center. A dummy dee may include a rectangular metal wall witha slot that is spaced near to the exposed rim of the active dee. In someimplementations, the dummy dee is connected to a reference voltage atthe vacuum chamber and magnet yoke.

Applying RF voltage in the presence of a strong magnetic field can causemulti-pactoring, which can reduce the magnitude of the RF field and, insome cases, cause an electrical short. To reduce the amount ofmulti-pactoring, and thereby maintain the RF field, DC (direct current)bias voltage may be applied to the active dee and, in someimplementations, also to the dummy dee. In some implementations, thedifferential DC bias voltage between the active dee and dummy dee may becontrolled to reduce multi-pactoring and thereby increase beamintensity. For example, in some implementations, there may be a 50%differential between the DC bias voltage on the active dee and dummydee. In an example implementation, there is a −1.9 KV DC bias voltageapplied to the dummy dee and there is a −1.5 KV DC bias voltage beapplied to the active dee.

In another example technique, the intensity of the particle beam can becontrolled by controlling the rate at which the RF voltage is swept—forexample, the slope of the decrease. By decreasing the slope, it ispossible to increase the amount of time during which particles can beextracted from the plasma column. As a result, more particles can beextracted, thereby increasing the intensity of the particle beam. Theconverse is also true, e.g., by increasing the slope, the amount of timeduring which particles can be extracted from the plasma column can bedecreased, which can result in a decrease in particle beam intensity.

Implementations of the foregoing techniques for controlling the particlebeam intensity are described in U.S. Pat. No. 9,723,705 entitled“Controlling Intensity Of A Particle Beam”, the contents of which areincorporated herein by reference.

The control system may also control (1103) the spot size of the particlebeam. As indicated above, one or more scattering devices may be movedinto the path of the particle beam to change its spot size. Motors maybe used to control movement of the scattering devices. The motors may beresponsive to commands from the control system based on instructions inthe treatment plan. In some implementations, the native spot size of thesynchrocyclotron is the smallest spot size that is produced by thesystem. Since beam intensity is also a function of spot size, this spotsize also produces the greatest beam intensity. In some implementations,the spot size that is producible by the system is less than 2millimeters (mm) sigma. In some implementations, the spot size that isproducible by the system is at least 2 mm sigma. In someimplementations, the spot size that is producible by the system isbetween 2 mm sigma and 20 mm sigma. In some implementations, the spotsize that is producible by the system is greater than 20 mm sigma. Insome implementation, operation 1103 may be omitted.

The control system controls (1104) the scanning magnet to move theparticle beam in accordance with the treatment plan to a path 24 throughtarget 21, as shown in FIG. 2 for example. Controlling the scanningmagnet may include controlling the current through the coils of thescanning magnet (FIGS. 6 and 7 ) that control movement of the particlebeam in the Cartesian X dimension, controlling the current through coilsof the scanning magnet that control movement of the particle beam in theCartesian Y dimension, or both. At that location, the system delivers anultra-high dose rate of radiation to a column that extends along thebeam path through the target. In this example, the column includesinterior portions of the target that are located along a direction 29 ofthe particle beam (FIG. 2 ). Column 25 is three dimensional in that itextends radially from the center of the beam spot to a perimeter of thespot and the column extends downward through the target. In someimplementations, the column extends through the entirety of the targetas shown in FIG. 2 . In some implementations, the column extends onlypart-way through the target. In some implementations the column isentirely within an interior of the target. In some implementations, thecolumn starts at one surface of the target and extends to an interior ofthe target but does not reach the other surface of the target. In someimplementations, parts of adjacent columns overlap.

The column is treated (1105) using an ultra-high dose rate of radiation.Examples of ultra-high dose rates of radiation are described herein andinclude, but are not limited to, 1 Gray-per-second or more for aduration of less than 5 s. The control system controls the energy of theparticle beam while the particle beam is stationary so that the particlebeam treats the column in the target. Treating the column in the targetincludes changing the energy of the particle beam so that, for eachchange in energy a majority of a dose of protons in the particle beam(its Bragg peak) deposits at a different depth within the target. Asdescribed herein, the energy of the particle beam may be changed bymoving structures, which may be made of boron carbide, into or out ofthe path of the particle beam, as shown in the examples of FIGS. 12 to19 and 33 to 42 . All or some of the operations of FIG. 11 may berepeated to treat different columns on an irradiation target. Forexample operations 1102, 1103, 1104, and 1105 may be repeated for eachcolumn to be treated on an irradiation target.

In implementations described below that use a variable-energysynchrocyclotron (or other type of variable energy particleaccelerator), the energy of the particle beam may be changed by changingthe current through the main coils of the synchrocyclotron. In someimplementations, the energy of the particle beam is changed by movingstructures, such as the energy-absorbing plates of range modulator 460,into and out of the path of the particle beam. In this regard, since thetreatment plan specifies the locations of the columns on the target, theenergy-absorbing plates of the range modulator may be pre-positionedproximate to those locations so as to reduce the time it takes for thoseplates to move into and out of position. Referring to FIG. 12 , forexample, plates 500—which may be made from pure boron carbide or a boroncarbide composite, for example—may be positioned proximate to column 501in target 503 before treatment of column 501 with radiation begins. Theplates may be moved from that location into the particle beam, therebyreducing the distance that the plates need to travel. That is, plates500 may be configured to retract fully into the range modulator. Theplates may be extended partially or fully prior to treatment and, as aresult, need not travel from their fully retracted position in order toreach the path of the particle beam.

One or more of the plates may be controlled to move into and out of thepath of the particle beam to change the energy of the particle beam, asnoted. In an example, each of the one or more plates is movable into orout of the path of the particle beam in a duration of 100 ms or less. Inan example, each of the one or more plates is movable into or out of thepath of the particle beam in a duration of 50 ms or less. In an example,each of the one or more plates is movable into or out of the path of theparticle beam in a duration of 20 ms or less. Use of linear motors, asdescribed previously, may promote rapid movement of the plates, althoughelectrical motors may be used as well. In this example, rapid movementincludes movement on the order of tens of milliseconds.

One or more of the plates may be moved into and out of the path of theparticle beam based on sequences defined in the treatment plan. Forexample, referring to FIGS. 12, 13, 14, and 15 , a particle beam 504 ispositioned by the scanning system to treat column 501 of target 503 atan ultra-high dose rate. In this example, to treat progressivelyshallower portions of column 501, treatment initially is performed withno plate in the path of the particle beam. This is shown in FIG. 12 .The deepest part 502 of column 501 therefore is treated. In FIG. 13 ,plate 500 a proceeds into the path of particle beam 504 along thedirection of arrow 505 to reduce the energy of the particle beam. Inthis plate configuration, the second deepest part 506 of column 501 istreated. In FIG. 14 , plate 500 b also proceeds into the path ofparticle beam 504 along the direction of arrow 505 to reduce further theenergy of the particle beam. In this plate configuration, the thirddeepest part 508 of column 501 is treated. In FIG. 15 , plate 500 c alsoproceeds into the path of particle beam 504 along the direction of arrow505 to reduce further the energy of the particle beam. In this plateconfiguration, the shallowest part 510 of column 501 is treated. Bychanging the energy of particle beam 504 while particle beam 504 isstationary, the entirety of column 501 may be delivered ultra-high doserate radiation. Examples of ultra-high dose rates are provided herein.

The particle beam may be directed by the scanning magnet to a new paththrough the target to treat a different column of target 503. Thedifferent column may be immediately adjacent to column 501 or may not beimmediately adjacent to column 501. In some implementations, spots ofthe beam may overlap in part. For example, referring to FIGS. 16, 17,18, and 19 , a particle beam 604 is positioned by the scanning system totreat column 601 of target 503 at an ultra-high dose rate. In thisexample, to treat progressively deeper portions of column 601, treatmentinitially is performed with all plates 500 a, 500 b, and 500 c in thepath of the particle beam. This is shown in FIG. 16 . The shallowestpart 602 of column 601 therefore is treated first. In FIG. 17 , plate500 c moves out of the path of particle beam 604 along the direction ofarrow 605 to increase the energy of the particle beam. In this plateconfiguration, the second shallowest part 602 of column 601 is treated.In FIG. 18 , plate 500 b also moves out of the path of particle beam 604along the direction of arrow 605 to increase further the energy of theparticle beam. In this plate configuration, the third shallowest part608 of column 601 is treated. In FIG. 19 , plate 500 c also moves out ofthe path of particle beam 604 along the direction of arrow 605 toincrease further the energy of the particle beam. In this plateconfiguration, the deepest part 610 of column 601 is treated. Bychanging the energy of particle beam 604 while particle beam 604 isstationary, the entirety of column 601 may be delivered ultra-high doserate radiation.

In some implementations, the plates need not be sequenced in order totreat a column. For example, plate 500 a could be moved into the path ofthe particle beam first, followed by plate 500 c, followed by plate 500b.

During delivery of ultra-high dose rate radiation to column 501 or 601,the intensity of particle beam 504 or 604 may be changed as necessary inorder to deliver the ultra-high dose rate radiation specified in thetreatment plan. Notably, the particle beam is stationary during deliveryof the ultra-high dose rate radiation to each column. For example, whilethe ultra-high dose rate radiation is being delivered to differentdepths within the column, the path of the particle beam does not changerelative to the target and the particle beam does not move. After theultra-high dose rate radiation is delivered to the column, the particlebeam is directed on a new path through the target in accordance with thetreatment plan. Ultra-high dose rate radiation is then applied at thatnew path in accordance with the treatment plan in the same manner asdescribed with respect to FIG. 11 . This process is repeated until allof the target is treated using the ultra-high dose rate radiation oruntil a designated part of the target is treated using the ultra-highdose rate radiation. In some implementations, the columns may beparallel as shown in the figures, with some overlap in someimplementations. In some implementations, at least some of the columnsmay not be in parallel resulting in overlap. In some implementations,sets of columns may be applied to the same target or micro-volume fromdifferent angles, thereby treating the target multiple times withradiation while preventing healthy tissue from being impacted byradiation more than once.

In some implementations, the particle beam is never again directed alongpaths that have already been treated using the ultra-high dose rateradiation. For example, the particle beam steps from path to paththrough target 503. In this example, each column extending into thetarget along a path is treated using the ultra-high dose rate radiationonly once. Columns are not revisited and treated again. By treatingcolumns only once using ultra-high dose rate radiation, healthy tissueabove, and in some cases below, the target is less susceptible to damagefrom the radiation. Notably, however, the example systems describedherein are not limited to treating each column only once using theultra-high dose rate radiation. For example, in some implementations,each column may be revisited any appropriate number of times andsubjected to one or more additional doses of ultra-high dose rateradiation. Furthermore, the example systems described herein are notlimited to treating each column using only ultra-high dose rateradiation. For example, columns of a target may be treated as describedherein using dose rates of radiation that are less than what would beconsidered an ultra-high dose rate. For instance, columns of a targetmay be treated as described herein using dose rates of radiation such as0.1 Gray-per-second for a duration of one or more minutes. In someimplementations, column-by-column treatment such as that shown in FIG. 2may be combined with layer-by-layer treatment such as that shown in FIG.1 . For example, the target may be treated column-by-column followed bylayer-by-layer or treated layer-by-layer followed by column-by-column.In some implementations, part of the target may be treatedcolumn-by-column and part of the target may be treated layer-by-layer ineach case with ultra-high dose rate radiation or less.

In some implementations, energy-absorbing plates of the range modulatormay be sequenced differently for different columns on the target inorder to reduce treatment time. For example, for a column 501, theplates may be moved sequentially into the particle beam as explainedwith respect to FIGS. 12 to 15 . Then, the particle beam may be directedto treat an adjacent—or other—column 601 of the target. If the platesalready cover that path of the particle beam, they may be movedsequentially out of the path of the particle beam as described withrespect to FIGS. 16 to 19 . If the plates do not already cover that pathof the particle beam, the plates may be moved together to cover thatpath of the particle beam and then moved sequentially out of the path ofthe particle beam. Accordingly, for a first column, the plates may bemoved sequentially to treat progressively shallower portions—forexample, layers—of the first column. For a second column that isadjacent to the first column, the plates the plates may be movedsequentially to treat successively deeper portions—for example,layers—of the second column. This process may be repeated throughout thetarget for adjacent paths of the particle beam. In some implementations,movements of the plates may be incremental in the beam field; forexample, based on the spot size (e.g., on the order of millimeters)rather than from their fully retracted position. For example, the platesmay be moved from particle beam path to adjacent particle beam pathrather than being fully retracted and extended for each column.

In some implementations, the energy-absorbing plates are movable acrossall or part of the beam field. In some examples, the beam field is themaximum extent that the beam can be moved across a plane parallel to thetreatment area on a patient. One or more of the plates may track theparticle beam as it moves from particle beam to adjacent particle beam.For example, one or more of the plates may move along with movement ofthe particle beam such that the particle beam passes through one or moreof the plates while the plates move.

In some implementations, a dose of radiation that is less than anultra-high (or FLASH) dose rate radiation may be applied to the targetlayer-by layer using an energy degrader having structures such asplates, polyhedra, or curved three-dimensional shapes that are made ofboron carbide. For example, referring to FIG. 1 , an entire layer 10 ofa target 11 may be treated using a particle beam 12 having an energysufficient to deliver dose to layer 10 by moving the particle beamacross the layer along the directions of arrows 15. The energy degradermay then be reconfigured—for example, a plate made of boron carbide maybe moved out of the beam path to increase an energy level of theparticle beam. Then a different layer 16 of the target 11 may be treatedin the same manner using a particle beam having a different energysufficient to deliver dose to layer 16, and so on.

In some implementations, FLASH doses of radiation may be delivered alonga single column, with the beam direction fixed at a single spot at anisocenter of the particle accelerator. In some implementations, FLASHdoses of radiation may be delivered using slightly larger localizedvolumes—referred to as micro-volumes—rather than columns aimed at asingle spot. A micro-volume may be a voxel, part of a voxel, or includemultiple voxels as specified in the treatment plan. FIGS. 33 to 42 showan example of delivery of radiation by column using FLASH dose rates tomicro-volumes of an irradiation target. Examples of FLASH dose rates aredescribed herein. In some implementations, delivery of radiation bycolumn to the micro-volumes of FIGS. 33 to 42 may be at non-FLASH doserates or combined FLASH dose rates and non-FLASH dose rates.

FIG. 33 shows an example of part 1400 of an irradiation target, such asa tumor in a patient. Part 1400 is broken into four micro-volumes 1401,1402, 1403, and 1404. Although cubical micro-volumes are shown, themicro-volumes may have any appropriate shape, such as three-dimensionalorthotopes, regular curved shapes, or amorphous shapes. In this example,each micro-volume is treated through delivery of radiation by column inthe manner described herein, for example with respect to FIGS. 12 to 19. For example, column depths of a micro-volume may be treated withradiation by using energy degrader plates to change the beam energy orby controlling a variable-energy synchrocyclotron to change the beamenergy. After an individual micro-volume has been treated, the nextmicro-volume is treated, and so forth until the entire irradiationtarget has been treated. Treatment of the micro-volumes may be in anyappropriate order or sequence.

In the example of FIGS. 33 to 42 , only eight columns 1405 are shown.However, any appropriate number of columns may be treated permicro-volume. In some examples 10 to 20 spots, and thus columns, maytreat a micro-volume. In addition, although each spot corresponds to acolumn of radiation, only the front columns are shown in the figures forclarity. Furthermore, although the example described herein treats themicro-volumes from the most deep part of the column to the most shallowpart of the column, that need not be the case. For example, energydegrader plates may be controlled to treat one micro-volume from themost deep part of columns to the most shallow part of the columns andthen treat the neighboring micro-volume from the most shallow part ofthe columns to the most deep part of the columns and so forth, asdescribed with respect to FIGS. 12 to 19 . In other examples, differentcolumn depths may be treated non-sequentially.

In FIG. 33 , the deepest parts 1407 of columns 1405 are treated.

Treated parts of the columns are shaded and untreated parts are notshaded, as is the convention herein. In FIG. 34 , the next deepest parts1408 of columns 1405 are treated. In FIG. 35 , the next deepest parts1409 of columns 1405 are treated. In FIG. 36 , the next deepest parts1410 of columns 1405 are treated. In FIG. 37 , the shallowest parts 1411of columns 1405 are treated, thereby completing treatment ofmicro-volume 1401. In this regard, although the columns are separatedfor clarity, the columns may actually overlap at least in part as is thecase with respect to FIGS. 12 to 19 to ensure that the entiremicro-volume is treated with radiation.

After micro-volume 1401 is treated, the next micro-volume 1402 istreated in a similar manner. In FIG. 38 , the deepest parts 1417 ofcolumns 1415 are treated. In FIG. 39 , the next deepest parts 1418 ofcolumns 1415 are treated. In FIG. 40 , the next deepest parts 1419 ofcolumns 1415 are treated. In FIG. 41 , the next deepest parts 1420 ofcolumns 1415 are treated. In FIG. 42 , the shallowest parts 1421 ofcolumns 1415 are treated, thereby completing treatment of micro-volume1402. As was the case above, although the columns are separated forclarity, the columns may actually overlap at least in part as is thecase with respect to FIGS. 12 to 19 to ensure that the entiremicro-volume is treated with radiation.

After micro-volume 1402 is treated, the remaining micro-volumes may betreated in a similar manner. The micro-volumes may be treated in anyorder or sequence and using any appropriate number and placement ofcolumns. In addition, as described herein, individual columns may betreated using different beam intensities. These intensities may varyfrom column-to-column, from micro-volume-to-micro-volume or both fromcolumn-to-column and from micro-volume-to-micro-volume. Furthermore,each micro-volume may be treated from multiple different angles as partof intensity-modulated proton therapy treatment (IMPT).

In an example, plots of FIGS. 43A and 43B show the results of MonteCarlo simulations that calculate radiation dose delivered to a treatmentvolume as well as the time it takes for each voxel in that dosecalculation to reach the final dose. In an example, applying performancemodifications to some parameters of a synchrocyclotron—for example, 10ms or less layer switching time instead of 50 ms layer switching time,increasing the beam current, and enhancing pulse-pulse stability—spotsdelivered on a cube that is 3 cm on each side can be delivered withevery part of the treatment volume receiving its dose in less than 500ms. These small cubes were not strictly delivered in columns where eachenergy layer has a single spot, but rather in micro-volumes where eachlayer has a few (e.g., 10 to 20) spots. In addition, collimation may beused to isolate one micro-volume from another, allowing these volumes tobe delivered in a reasonable amount of total treatment time. Forexample, the configurable collimator described herein or any otherappropriate collimating device, including standard multi-leafcollimators (MLC), may be used.

In some implementations, each micro-volume may be treated in the mannerdescribed with respect to FIGS. 12 to 19 . For example, the entirety ofa column in a micro-volume may be treated before moving on to a nextcolumn in the same micro-volume. Once all columns are treated in amicro-volume, then treatment proceeds to the next micro-volume. There,treatment is repeated until all columns of the micro-volume are treated.Treatment then proceeds to the next micro-volume and so on until theentire irradiation target is treated. These implementations differ fromthe implementations of FIGS. 33 to 42 in which an entire depth—ormicro-layer—of each column in a micro-volume is treated at once forevery column in that micro-volume. Thereafter, treatment proceeds to thenext depth and so forth until all columns in the micro-volume have beentreated.

Delivering radiation at ultra-high dose (FLASH) rates to all or part ofa column as described herein may be implemented to deposit doses ofradiation in any random manner. For example, referring to FIG. 32 , anexample column 1299 in a radiation target may be comprised of multipledepths. Each depth may comprise a micro-layer of the target that hasabout the diameter of a spot of the particle beam. Using delivery orradiation by column as described herein, radiation may be delivered toeach of depths 1301, 1302, and 1303 at ultra-high dose (FLASH) rates.Doses may be delivered in any manner established by the treatment plan.For example, a higher dose of radiation may be applied to depth 1303than to depths 1301 or 1302. In another example, the highest dose may beapplied to depth 1303, the next highest dose may be applied to depth1302, and the lowest dose may be applied to depth 1302. In anotherexample, the highest dose may be applied to depth 1301, the next highestdose may be applied to depth 1303, and the lowest dose may be applied todepth 1302. Thus, doses may be applied without regard to—for example,independent of—the shape of a Bragg peak produced by summing themultiple doses. In other words, in some cases, the doses may not beconfigured to obtain a spread-out Bragg peak along a column of radiationdelivered to an irradiation target at ultra-high dose (FLASH) rates orat lower dose rates.

In some implementations, one or more ridge filters or range modulatorwheels may be added into the path of the particle beam to spread out—forexample, to elongate—the Bragg peak of the particle beam. An elongatedor spread-out Bragg peak is created by using a uniform depth-dose curve.That is, the dose is calibrated based on the depth in the tissue towhich the dose is to be delivered in order to achieve an elongated Braggpeak that is flat or substantially flat. Referring to FIG. 32 , forexample, to achieve a spread-out Bragg peak such as 1300 using deliveryof radiation by column, a full (100%) dose may be applied to depth 1301in column 1299 of an irradiation target for a period of time. Next, an80% dose may be applied to depth 1302 for a period of time. Depth 1302is up-beam (that is, more shallow) than depth 1301. Next, a 66% dose maybe applied to depth 1303 for a period of time. Depth 1303 is up-beam(that is, more shallow) than depth 1302. This may be repeated untilspread-out Bragg peak 1300 is achieved.

Motors may control movement of the one or more ridge filters or rangemodulator wheels into or out of the path of the particle beam. Themotors may be responsive to command of the control system. Spreading outthe Bragg peak of the particle beam may be used for both columnartreatment as shown in FIGS. 12 to 19 or layer-by-layer treatment asshown in FIG. 1 . In some implementations, the intensity of the particlebeam may be increased using techniques such as those described hereinwhen the Bragg peak is spread-out.

In some implementations, a range modulator wheel may be roboticallycontrolled to move in two dimensions or in three dimensions within thebeam field so as to track movement of the particle beam. For example,referring to FIG. 23 , the range modulator wheel may be roboticallycontrolled to move in the Cartesian X dimension 918 and Z dimension 917in the path of the particle beam. The range modulator wheel may havevarying thicknesses and may spin to change the Bragg peak of theparticle beam and thus the depth within the target at which a majorityof the particles are deposited. In some implementations, the rangemodulator wheel may include steps that define its various thicknesses.In some implementations, the intensity of the particle beam may becontrolled in order to control the dose delivered at each location onthe range modulator wheel. This may be done in order to controldepth-dose distributions.

As explained above, in some implementations, the scanning system doesnot include a configurable collimator. For example, in systems thatinclude boron carbide in the energy degrader, the spot size may be smalland precise enough to eliminate the need for a configurable collimator.However, in some implementations, the scanning system does include aconfigurable collimator. The configurable collimator may be controlledby the control system to trim the particle beam prior to the particlebeam reaching the irradiation target. As also explained, theconfigurable collimator may be controlled to trim a stationary particlebeam differently as the energy of that particle beam changes to treatdifferent portions—for example, depths—of a column in a target. Morespecifically, the cross-sectional area of the particle beam—in otherwords, the spot size of the particle beam—may change as the particlebeam passes through different amounts of tissue. To ensure that the sizeof the particle beam and thus the radius of the column being treatedremains consistent throughout the length of the column, theconfiguration of the collimator may be changed to provide differentamounts of trimming. In other words, the configuration of theconfigurable collimator may be changed in response to changes in theenergy of the particle beam. That is, since beams of different energypenetrate different amounts of tissue, those beams may experiencedifferent amounts of dispersion and therefore may require differentamounts of collimation to produce a regularly-shaped column such as acolumn having a cylindrical shape with a constant radius.

In some implementations, the configurable collimator contains generallyflat structures, which are referred to as “plates” or “leaves”, andwhich are controllable to move into the beam or treatment area to blockpassage of some radiation and allow passage of other radiation. Asexplained above, there may be two sets of leaves that face each other.The sets of leaves are controllable to produce an opening of size andshape that is appropriate for treatment. For example, each set of leavesis configurable to define an edge that is movable into a path of theparticle beam so that a first part of the particle beam on a first sideof the edge is blocked by the leaves, and so that a second part of theparticle beam on a second side of the edge is not blocked by the leavesand is allowed to pass to the treatment area. In some implementationsthe leaves are connected to, are part of, or include, linear motors—oneper leaf—that are controllable to control movement of the leaves towardsor away from the treatment area to define the edge.

In some implementations, the linear motors are controllable to configurea set of leaves to define a first edge and to configure another set ofleaves to define a second edge that faces the first edge. The linearmotors used with the configurable collimator may have configurationssimilar or identical to the linear motors used with the range modulatorplates described with respect to FIG. 10 . For example, each of thelinear motors may include a movable component and a stationarycomponent. The stationary component includes a magnetic field generatorto generate a first magnetic field. An example of a magnetic fieldgenerator includes two stationary magnets that are adjacent and spacedapart and that have their poles aligned. The movable component includesone or more coils to conduct current to produce a second magnetic fieldthat interacts with the first magnetic field to cause the moveablecomponent to move relative to the stationary component. For example, themovable component may be a coil-carrying plate between the two magnetsthat make up the stationary component. When current passes through thecoil, that current produces a magnetic field that interacts with themagnetic field produced by the two magnets, and that causes the movablecomponent (e.g., the current-carrying plate) to move relative to the twomagnets. Because a leaf is attached to the movable component, the leafmoves along with the movable component. The linear motors of differentleaves may be controlled to control movement of the leaves, and thus todefine the edges of the configurable collimator described above.

As noted, in some implementations, a linear motor includes two magnetsthat are adjacent and spaced apart and that have their poles aligned,and a coil-carrying plate that is sandwiched between the two magnets andthat moves relative to the two magnets. This configuration allowsmultiple linear motors to be arranged in a row, each in close proximityto the next, as may be required to control leaves of the configurablecollimator. For example, in some implementations, the leaves are on theorder of millimeters thick (e.g., five millimeters or less). Leaves ofthis thickness enable relatively high precision edges; however, leavesof this thickness can make implementation using conventional motorsimpractical in some cases. However, the linear motors described hereinenable use of leaves having thicknesses of this magnitude. For example,the two stationary magnets shield the coil-carrying plate that movesbetween them, thereby controlling movement of the leaves. By shieldingthe coil-carrying plates from stray magnetic fields, it is possible tocontrol movement of the plates even when multiple coil-carrying platesand corresponding stationary magnets are close proximity to each other.

In some implementations, the control system, which may be comprised ofone or more processing devices, is programmed to control the linearmotors to thereby control positioning of leaves to define an edge. Forexample, the control system may be controllable to output one or morecontrol signals to control one or more of the linear motors to extend orto retract one or more of the leaves to define the edge. In someimplementations, motion of the linear motors may be tracked usingencoders. In some examples, encoders include electronic devices that areconnected to a same assembly as the leaves and the linear motors. Theencoders may include or more of laser sensors, optic sensors, or diodesensors. The encoders detect movement of the leaves, e.g., by detectingwhere markings or other indicia on the leaves, or on structures that areconnected to and that move with the leaves, are located relative to theencoders. Information about locations of the leaves is fed back to thecontrol system and is used by the control system to confirm the positionof the leaves during operation and, in some implementations, to changetheir position. The encoders may be, or include, simple electronicsensors that are not as sensitive to neutron radiation as the processingdevices above and that, therefore, may be located in the treatment room.

As noted previously, some implementations may not include a configurablecollimator. In example implementations such as these, the particle beampasses through the energy degrader and to the patient without subsequentconditioning such as collimation. For example, in implementations wherethe structures—such as plates, polyhedra, or curved three-dimensionalshapes—include boron carbide, the spot size of the beam may be reducedrelative to the spot size of the beam produced using other materials inthe energy degrader. In such cases, additional collimation may not benecessary to achieve the spot resolution needed to treat the irradiationtarget. As noted, in some implementations, a configurable collimator maybe between the energy degrader and the patient. Example implementationsof a configurable collimator that may be used are described with respectto FIGS. 20 to 25 .

FIG. 20 shows an example of a leaf 740 that may be used in theconfigurable collimator, although the configurable collimator is notlimited to use with this type of leaf. The height 750 of the leaf isalong the beam line (e.g., the direction of the particle beam). Thelength 752 of the leaf is along its direction of actuation into and outof the treatment area, and is based on the field size, or portionthereof, that the system can treat. The field size corresponds to thetreatment area that the beam can impact. The width 753 of the leaf isthe direction along which multiple leaves stack when actuated.Generally, the more leaves that are used, the higher the resolution ofthe aperture that can be produced, including for curved boundaries.

In FIG. 20 , leaf 740 includes a tongue and groove feature 755 along itsside, which is configured to reduce inter-leaf leakage when multiplesuch leaves stack. In this example, the curved end 756 of leaf 740 isconfigured to maintain a surface tangent to the beam at all locations inthe treatment area. However, the end of each leaf may be flat, notcurved.

In some implementations, the configurable collimator leaves have aheight that is sufficient to block at least the maximum beam energy(e.g., the maximum energy of the particle beam output by theaccelerator). In some implementations, the configurable collimatorleaves have a height that blocks less than the maximum beam energy. Insome implementations, the configurable collimator leaves have lengthsthat are dictated not by the area of an entire treatment area, butrather by the area of a single beam spot (the cross-sectional area ofthe particle beam) or multiple beam spots.

FIG. 21 shows an example implementation of part a configurablecollimator 800. Configurable collimator 800 includes leaves 801 having aheight and made of a material, such as nickel, brass, tungsten, or othermetal, sufficient to inhibit or prevent passage of radiation at a givenenergy. For example in some systems, a particle accelerator isconfigured to generate a particle beam having a maximum energy of 100MeV (million electron-volts) to 300 MeV. Accordingly, in such systems,the leaves may be constructed to prevent passage of a beam having anenergy of 100 MeV, 150 MeV, 200 MeV, 250 MeV, 300 MeV, and so forth. Forexample in some systems, a particle accelerator is configured togenerate a particle beam having a maximum energy that exceeds 70 MeV.Accordingly, in such systems, the leaves may be constructed to preventpassage of a beam having an energy of 70 MeV or more.

Leaves 801 are mounted on carriages to control their movement relativeto a treatment area of an irradiation target, such as a cross-sectionallayer of a tumor in a patient. The movement is controlled to causeleaves 801 to cover some parts of treatment area 804, thereby preventingradiation from impacting those parts during treatment, while leavingother parts of treatment area exposed to the radiation. In the exampleimplementation of FIG. 21 , there are fourteen leaves in total, seven onthe left and seven on the right. In some implementations, there may be adifferent number of leaves, e.g., ten in total, five on the left andfive on the right, twelve in total, six on the left and six on theright, and so forth.

In FIG. 21 , locations 802 represent centers of beam spots and thus thelocations of columns in the target to which radiation is to bedelivered. Circle 808 represents parts of a treatment boundary beyondwhich no radiation is intended to be delivered. Beam spots that areclose to this boundary (e.g., within one standard deviation of theparticle beam's profile) border healthy tissue. These spots may betrimmed (that is, blocked) by appropriate configuration and placement ofleaves on the configurable collimator. An example of a beam spot to betrimmed is beam spot 811, having its center at location 806. As shown,leaves 801 are configured to block the portion of beam spot 811 thatextends beyond circle 808 and into healthy tissue (or at least tissuenot designated for treatment).

In an example implementation, on each of two separate carriages, thereare five leaves that are about 5 mm in width and two leaves that areabout 80 mm in width. In some implementations, on each of two separatecarriages, there are seven leaves, two of which each have widths thatare three times or more the widths of each of five other leaves. Otherimplementations may contain different numbers, sizes, and configurationsof leaves, and different numbers and configurations of carriages. Forexample, some implementations may include any number between five andfifty leaves per carriage, e.g., 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15,16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33,34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, or 50leaves (or more) per carriage.

The carriages can move both horizontally and vertically, as describedherein. The leaves are also movable horizontally relative to eachcarriage into, and out of, the treatment area. In this way, the leavesare configurable to approximate the shape of the treatment boundary inthe region near the area being treated (e.g., circle 811 or a portionthereof in this example).

The leaves may be moved vertically and/or horizontally between differentcolumns to be treated so that the leaves are in appropriate positionswhen the beam is delivered to a particular column. As noted, the leavesmay be reconfigured while the beam is stationary and based on beamenergy to provide different configurations for different beam energies.As explained, the beam may disperse somewhat in tissue. The configurablecollimator may be reconfigured as beam energy changes to maintain aregularly (e.g., cylindrically) shaped column.

FIGS. 22, 23, and 24 show an example implementation of a configurablecollimator, including carriages 913, 914, 915 configured to hold, and tomove, the leaves described above both vertically and horizontallyrelative to the treatment target. As shown, vertical movement includesmovement in the Cartesian Z-dimension 917, and horizontal movementincludes movement in the Cartesian X dimension 918 (with the Cartesian Ydimension being into, or out of, the page in FIG. 23 ). FIGS. 23 and 24show parts of carriage housings as transparent in order to showcomponents inside the housings; however, the housings are not actuallytransparent.

Carriage 913 is referred to herein as the primary carriage, andcarriages 914 and 915 are referred to herein as secondary carriages.Secondary carriages 914, 915 are coupled to primary carriage 913, asshown in FIGS. 22 to 24 . In this example, secondary carriages 914, 915each include a housing that is fixed to primary carriage 915 via acorresponding member 918, 919. In this example, primary carriage 913 ismovable vertically (the Z dimension) relative to the irradiation targetand relative to particle accelerator along tracks 920. The verticalmovement of primary carriage 913 also causes the secondary carriages tomove vertically. In some implementations, the secondary carriages movevertically in concert. In some implementations, vertical movement ofeach secondary carriage is independent of vertical movement of the othersecondary carriage.

As shown in FIGS. 22 to 24 , each secondary carriage 914, 915 isconnected to a corresponding rod or rail 922, 923, along which thesecondary carriage moves. More specifically, in this example, motor 925drives secondary carriage 914 to move along rod 922 towards or away fromsecondary carriage 915. Likewise, in this example, motor 926 drivessecondary carriage 915 to move along rod 923 towards or away fromsecondary carriage 914. Control over movement of the primary andsecondary carriages is implemented to position the leaves relative tothe irradiation target, as described herein. In addition, the leavesthemselves are also configured to move in and out of the carriages, asalso described herein.

As shown in FIG. 24 , a motor 930 drives the vertical movement ofprimary carriage 913. For example, as shown in FIG. 24 , lead screw 931is coupled to housing 932, which holds motors 925, 926 that drivecorresponding secondary carriages 914, 915, and which is mounted ontracks 920. Lead screw 931 is coupled to, and driven vertically by,motor 930. That is, motor 930 drives lead screw 931 vertically (theCartesian Z dimension). Because lead screw 931 is fixed to housing 932,this movement also causes housing 932, and thus secondary carriages 914,915, to move along tracks 920, either towards or away from theirradiation target.

In this example implementation, as noted, seven leaves 935, 936 aremounted on each secondary carriage 914, 915. Each secondary carriage maybe configured to move its leaves horizontally into, or out of, thetreatment area. The individual leaves on each secondary carriage may beindependently and linearly movable using linear motors in the Xdimension relative to other leaves on the same secondary carriage. Insome implementations, the leaves may also be configured to move in the Ydimension. Furthermore, the leaves on one secondary carriage 914 may bemovable independently of the leaves on the other secondary carriage 915.These independent movements of leaves on the secondary carriages,together with the vertical movements enabled by the primary carriage,allow the leaves to be moved into various configurations. As a result,the leaves can conform, both horizontally and vertically, to treatmentareas that are randomly shaped both in horizontal and verticaldimensions. The sizes and shapes of the leaves may be varied to createdifferent conformations. For example, the sizes and shapes may be variedto treat a single beam spot and, thus, a single column. In someimplementations individual leaves on each secondary carriage may beindependently and linearly movable using electric motors that drive leadscrews in the X dimension relative to other leaves on the same secondarycarriage.

The leaves may be made of any appropriate material that prevents orinhibits transmission of radiation. The type of radiation used maydictate what material(s) are used in the leaves. For example, if theradiation is X-ray, the leaves may be made of lead. In the examplesdescribed herein, the radiation is a proton or ion beam. Accordingly,different types of metals or other materials may be used for the leaves.For example, the leaves may be made of nickel, tungsten, lead, brass,steel, iron, or any appropriate combinations thereof. The height of eachleaf may determine how well that leaf inhibits transmission ofradiation.

In some implementations, the leaves may have the same height, whereas inother implementations, some of the leaves may have heights that aredifferent from heights of others of the leaves. For example, a set ofleaves may each be 5 mm in height. However, any appropriate heights maybe used. For example, leaves 935, 936 may have any of the following (orother heights): 1 mm, 2 mm, 3 mm, 4 mm, 5 mm, 6 mm, 7 mm, 8 mm, 9 mm, 10mm, 11 mm, 3 mm, 13 mm, 14 mm, 15 mm, 16 mm, 17 mm, 18 mm, 19 mm, 20 mm,21 mm, 22 mm, 23 mm, 24 mm, 25 mm, 26 mm, 27 mm, 28 mm, 29 mm, and soforth. The leaves may have any combination of the foregoing heights. Inaddition, each of the leaves may have a different height than one ormore others of the leaves.

In some implementations, the leaves have heights that are enough notonly to fully stop a particle beam at the maximum expected proton energy(e.g., 3.3 cm of Tungsten at 230 MeV or, e.g., 5.2 cm of nickel), butalso to have enough extra material to prevent proton transmissionbetween the leaves. This material may have a tongue and groove structureas shown in FIG. 20 , or a similar configuration. The leaf ends may beconfigured to include curved or tapered surfaces to enhance deliveredpenumbra for proton beams of various divergence.

In some implementations, there may be more than one primary carriage andcorresponding motors and rails. For example, a first primary carriagemay control vertical movement of a first secondary carriage, and asecond primary carriage may control vertical movement of a secondsecondary carriage. Therefore, in such implementations, the twosecondary carriages can be moved independently in the verticaldimension, if desired. In any case, the primary carriage may be computercontrolled. For example, executable instructions are stored in computermemory (e.g., one or more non-transitory machine-readable storagemedia), and executed by one or more processing devices to control themovement. Control may be performed with, or without, user input duringtreatment.

As explained, each secondary carriage 914, 915 includes a correspondingmotor to control horizontal carriage movement, as described above. Insome implementations, all leaves on a single carriage are independentlymovable using linear motors—with one linear motor controlling each leaf.Each leaf may be controlled by a linear motor of the type described inFIG. 10 to create an edge to block at least some radiation from reachingthe patient, e.g., to trim one or more spots produced by the particlebeam. As noted, a linear motor used in the configurable collimator mayhave the same structure and function as a linear motor used with therange modulator. In this case, however, the collimator leaf is attachedto the linear motor instead of an energy-absorbing plate. Each linearmotor drives its corresponding leaf linearly to reach its position in aconfigured edge.

In the example implementations described above, each leaf isindependently actuated using a separate, and independently-controllable,linear motor such that any appropriate shape can be traced with a leafconfiguration. It may be, however, that such flexibility is not requiredto achieve acceptable edge conformality. The leaves could bemechanically constrained with the ability to achieve only a finitenumber of configurations. For example, the leaves could be restricted toarrangements that put them in a vertical line, forward diagonal shape,backward diagonal shape, concave shape, convex shape, or any otherachievable shape. In this way, flexibility could be traded formechanical simplicity.

In some cases, better beam performance (penumbra or edge sharpness)results when the particle beam is tangent to the surface of a leaf edge.However, since the beam effectively originates from a single pointsource, the angle with which it passes through the plane of theconfigurable collimator changes as the beam is moved away from thecenter of the field. For this reason, leaves may have curved edges, asshown in FIG. 20 , so that the edges can always be placed a locationthat makes them tangent to the particle beam. In an exampleimplementation of the configurable collimator, the tracks on which bothprimary and secondary carriages move are curved so that flat leaf edgescan be used in lieu of curved leaf edges, and so that the flat butremain tangent to the particle beam.

To summarize, in some implementations, the configurable collimator mayhave a relatively small size, at least in part due to the linear motorsdescribed herein. Thus, in contrast to standard multi-leaf collimators,an example configurable collimator may therefore be used to trim afraction of a treatment area at one time, e.g., an area that is lessthan the entire treatment area and that is about equal to one spot size,two spot sizes, three spot sizes, four spot sizes, five spot sizes, andso forth. Thus, in some implementations, the configurable collimator maybe small enough to trim a single spot at once and may be large enough totrim several spots in one position, but not the entire field withoutmoving. As noted, the ability to trim a single spot may be used tomaintain a regular shape of a treatment column as the energy of theparticle beam used to create that column varies.

The scanning system may include the configurable collimator describedherein, which is placeable relative to the irradiation target to limitthe extent of the particle beam. For example, the configurablecollimator may be placed in the beam path down-beam of the energydegrader and before the particle beam hits the treatment area of theirradiation target. The configurable collimator is controllable by thecontrol system and in accordance with the treatment plan to allow theparticle beam to pass therethrough and then hit certain parts of thetreatment area, while preventing the particle beam from hitting otherparts of the patient. FIG. 25 depicts placement of an implementation ofthe configurable collimator 970 relative to a patient 971. The directionof beam 971 a is also shown.

An example of a configurable collimator that may be used is described inU.S. Patent Publication No. 2017/0128746 entitled “Adaptive Aperture”,the contents of which are incorporated herein by reference.

FIGS. 26 and 27 show parts of an example of a proton therapy system 1082containing a particle accelerator mounted on a gantry. Because theaccelerator is mounted on the gantry it is in or adjacent to thetreatment room. The particle accelerator may be the synchrocyclotron ofFIG. 3 ; however, the system is not limited to use withsynchrocyclotrons. The gantry and the particle accelerator may becontrolled, along with the scanning system, in accordance with thetreatment plan to treat columns of an irradiation target usingultra-high dose rate radiation in the manner described herein. In someimplementations, the gantry is steel and has two legs (not shown)mounted for rotation on two respective bearings that lie on oppositesides of a patient. The gantry may include a steel truss (not shown)that is connected to each of its legs, that is long enough to span atreatment area in which the patient lies, and that is attached at bothends to the rotating legs of the gantry. The particle accelerator may besupported by the steel truss for motion around the patient.

In the example of FIGS. 26 and 27 , the patient is located on atreatment couch 1084. In this example, treatment couch 1084 includes aplatform that supports the patient. The platform also may include one ormore restraints (not shown) for holding the patient in place and forkeeping the patient substantially immobile during movement of the couchand during treatment. The platform may, or may not, be padded and/orhave a shape (e.g., an indentation) that corresponds to the shape ofpart of the patient. The couch may be moved via arm 1085.

FIG. 28 shows an example of the gantry configuration described in U.S.Pat. No. 7,728,311 incorporated herein by reference, and includescomponents of an alternative implementation of a proton therapy systemthat usable to treat columns of an irradiation target using ultra-highdose rate radiation in the manner described herein. The example protontherapy system of FIG. 28 includes an inner gantry 1190 having a nozzle1191, a treatment couch 1192, and a particle accelerator 1193 (e.g., asynchrocyclotron of the type described herein) mounted on an outergantry 1194 for rotation at least part-way around the patient to deliverradiation to target(s) in the patient. Treatment couch 1192 iscontrollable in accordance with the treatment plan and configured torotate and to translate the patient in the manner described herein.

In the example of FIG. 28 , particle accelerator 1193 is also mounted toouter gantry 1194 also to enable linear movement (e.g., translationalmovement) of the particle accelerator in the directions of arrow 1195along arms 1196. As also shown in FIG. 28 , the particle accelerator1193 may be connected to a gimbal 1199 for pivoting motion relative tothe gantry. This pivoting motion may be used to position theaccelerator, and thus the beam, for treatment.

Components of the scanning system including the scanning magnet, the ionchamber, the range modulator, and the configurable collimator may bemounted on, in, or coupled to a nozzle 1081, 1191 of the proton therapysystem's inner gantry. These components may be controlled by the controlsystem in accordance with the treatment plan to treat columns of anirradiation target using ultra-high dose rate radiation. In bothexamples, the nozzle is movable along a track of the inner gantry (1080or 1190) relative to the patient and the particle accelerator, and isextensible towards, and retractable away from, the patient, thereby alsoextending and retracting the components mounted thereon.

In some implementations, the synchrocyclotron used in the proton therapysystem described herein may be a variable-energy synchrocyclotron. Insome implementations, a variable-energy synchrocyclotron is configuredto vary the energy of the output particle beam by varying the magneticfield in which the particle beam is accelerated. For example, thecurrent may be set to any one of multiple values to produce acorresponding magnetic field. In an example implementation, one or moresets of superconducting coils receives variable electrical current toproduce a variable magnetic field in the cavity. In some examples, oneset of coils receives a fixed electrical current, while one or moreother sets of coils receives a variable current so that the totalcurrent received by the coil sets varies. In some implementations, allsets of coils are superconducting. In some implementations, some sets ofcoils, such as the set for the fixed electrical current, aresuperconducting, while other sets of coils, such as the one or more setsfor the variable current, are non-superconducting (e.g., copper) coils.

Generally, in a variable-energy synchrocyclotron, the magnitude of themagnetic field is scalable with the magnitude of the electrical current.Adjusting the total electric current of the coils in a predeterminedrange can generate a magnetic field that varies in a corresponding,predetermined range. In some examples, a continuous adjustment of theelectrical current can lead to a continuous variation of the magneticfield and a continuous variation of the output beam energy.Alternatively, when the electrical current applied to the coils isadjusted in a non-continuous, step-wise manner, the magnetic field andthe output beam energy also varies accordingly in a non-continuous(step-wise) manner. The scaling of the magnetic field to the current canallow the variation of the beam energy to be carried out relativelyprecisely, thus reducing the need for an energy degrader. An example ofa variable-energy synchrocyclotron that may be used in the particletherapy systems described herein is described in U.S. Pat. No. 9,730,308entitled “Particle Accelerator That Produces Charged Particles HavingVariable Energies”, the contents of which are incorporated herein byreference.

In implementations of the particle therapy system that use avariable-energy synchrocyclotron, controlling the energy of the particlebeam to treat a column of the target may be performed in accordance withthe treatment plan by changing the energy of the particle beam output bythe synchrocyclotron. In such implementations, a range modulator may ormay not be used. For example, controlling the energy of the particlebeam may include setting the current in the synchrocyclotron main coilsto one of multiple values, each which corresponds to a different energyat which the particle beam is output from the synchrocyclotron. A rangemodulator may be used along with a variable-energy synchrocyclotron toprovide additional changes in energy, for, example, between discreteenergy levels provided by the synchrocyclotron.

In some implementations, a particle accelerator other than asynchrocyclotron may be used in the particle therapy system describedherein. For example, a cyclotron, a synchrotron, a linear accelerator,or the like may be substituted for the synchrocyclotron describedherein. Although a rotational gantry has been described (e.g., the outergantry), the example particle therapy systems described herein are notlimited to use with rotational gantries. Rather, a particle acceleratormay be mounted, as appropriate, on any type of robotic or othercontrollable mechanism(s)—characterized herein also as types ofgantries—to implement movement of the particle accelerator. For example,the particle accelerator may be mounted on or more robotic arms toimplement rotational, pivotal, and/or translational movement of theaccelerator relative to the patient. In some implementations, theparticle accelerator may be mounted on a track, and movement along thetrack may be computer-controlled. In this configuration, rotationaland/or translational and/or pivotal movement of the accelerator relativeto the patient can also be achieved through appropriate computercontrol. In some implementations, the particle accelerator may bestationary and located outside the treatment room, with the beam beingdelivered to a nozzle in the treatment room.

In some examples, as noted above, ultra-high dose rates of radiation mayinclude doses of radiation that exceed 1 Gray-per-second for a durationof less than 500 ms. In some examples, ultra-high dose rates ofradiation may include doses of radiation that exceed 1 Gray-per-secondfor a duration that is between 10 ms and 5 s. In some examples,ultra-high dose rates of radiation may include doses of radiation thatexceed 1 Gray-per-second for a duration that is less than 5 s.

In some examples, ultra-high dose rates of radiation include doses ofradiation that exceed one of the following doses for a duration of lessthan 500 ms: 2 Gray-per-second, 3 Gray-per-second, 4 Gray-per-second, 5Gray-per-second, 6 Gray-per-second, 7 Gray-per-second, 8Gray-per-second, 9 Gray-per-second, 10 Gray-per-second, 11Gray-per-second, 12 Gray-per-second, 13 Gray-per-second, 14Gray-per-second, 15 Gray-per-second, 16 Gray-per-second, 17Gray-per-second, 18 Gray-per-second, 19 Gray-per-second, 20Gray-per-second, 30 Gray-per-second, 40 Gray-per-second, 50Gray-per-second, 60 Gray-per-second, 70 Gray-per-second, 80Gray-per-second, 90 Gray-per-second, or 100 Gray-per-second. In someexamples, ultra-high dose rates of radiation include doses of radiationthat exceed one of the following doses for a duration that is between 10ms and 5 s: 2 Gray-per-second, 3 Gray-per-second, 4 Gray-per-second, 5Gray-per-second, 6 Gray-per-second, 7 Gray-per-second, 8Gray-per-second, 9 Gray-per-second, 10 Gray-per-second, 11Gray-per-second, 12 Gray-per-second, 13 Gray-per-second, 14Gray-per-second, 15 Gray-per-second, 16 Gray-per-second, 17Gray-per-second, 18 Gray-per-second, 19 Gray-per-second, 20Gray-per-second, 30 Gray-per-second, 40 Gray-per-second, 50Gray-per-second, 60 Gray-per-second, 70 Gray-per-second, 80Gray-per-second, 90 Gray-per-second, or 100 Gray-per-second. In someexamples, ultra-high dose rates of radiation include doses of radiationthat exceed one of the following doses for a duration that is less than5 s: 2 Gray-per-second, 3 Gray-per-second, 4 Gray-per-second, 5Gray-per-second, 6 Gray-per-second, 7 Gray-per-second, 8Gray-per-second, 9 Gray-per-second, 10 Gray-per-second, 11Gray-per-second, 12 Gray-per-second, 13 Gray-per-second, 14Gray-per-second, 15 Gray-per-second, 16 Gray-per-second, 17Gray-per-second, 18 Gray-per-second, 19 Gray-per-second, 20Gray-per-second, 30 Gray-per-second, 40 Gray-per-second, 50Gray-per-second, 60 Gray-per-second, 70 Gray-per-second, 80Gray-per-second, 90 Gray-per-second, or 100 Gray-per-second.

In some examples, ultra-high dose rates of radiation include doses ofradiation that exceed one or more of the following doses for a durationof less than 500 ms, for a duration that is between 10 ms and 5 s, orfor a duration that is less than 5 s: 100 Gray-per-second, 200Gray-per-second, 300 Gray-per-second, 400 Gray-per-second, or 500Gray-per-second.

In some examples, ultra-high dose rates of radiation include doses ofradiation that are between 20 Gray-per-second and 100 Gray-per-secondfor a duration of less than 500 ms. In some examples, ultra-high doserates of radiation include doses of radiation that are between 20Gray-per-second and 100 Gray-per-second for a duration that is between10 ms and 5 s. In some examples, ultra-high dose rates of radiationinclude doses of radiation that are between 20 Gray-per-second and 100Gray-per-second for a duration that is less than 5 s. In some examples,ultra-high dose rate rates of radiation include doses of radiation thatare between 40 Gray-per-second and 120 Gray-per-second for a time periodsuch as less than 5 s. Other examples of the time period are thoseprovided above.

Operation of the example proton therapy systems described herein, andoperation of all or some component thereof, can be controlled (asappropriate), at least in part, using one or more computer programproducts, e.g., one or more computer programs tangibly embodied in oneor more non-transitory machine-readable media, for execution by, or tocontrol the operation of, one or more data processing apparatus, e.g., aprogrammable processor, a computer, multiple computers, and/orprogrammable logic components.

A computer program can be written in any form of programming language,including compiled or interpreted languages, and it can be deployed inany form, including as a stand-alone program or as a module, component,subroutine, or other unit suitable for use in a computing environment. Acomputer program can be deployed to be executed on one computer or onmultiple computers at one site or distributed across multiple sites andinterconnected by a network.

Actions associated with controlling all or part of the operations of theexample proton therapy systems described herein can be performed by oneor more programmable processors executing one or more computer programsto perform the functions described herein. All or part of the operationscan be controlled using special purpose logic circuitry, e.g., an FPGA(field programmable gate array) and/or an ASIC (application-specificintegrated circuit).

Processors suitable for the execution of a computer program include, byway of example, both general and special purpose microprocessors, andany one or more processors of any kind of digital computer. Generally, aprocessor will receive instructions and data from a read-only storagearea or a random access storage area or both. Elements of a computer(including a server) include one or more processors for executinginstructions and one or more storage area devices for storinginstructions and data. Generally, a computer will also include, or beoperatively coupled to receive data from, or transfer data to, or both,one or more machine-readable storage media for storing data, e.g.,magnetic, magneto-optical disks, or optical disks. Non-transitorymachine-readable storage media suitable for storing computer programinstructions and data include all forms of non-volatile storage area,including by way of example, semiconductor storage area devices, e.g.,EPROM, EEPROM, and flash storage area devices; magnetic disks, e.g.,internal hard disks or removable disks; magneto-optical disks; andCD-ROM and DVD-ROM disks.

Any two more of the foregoing implementations may be used in anappropriate combination with an appropriate particle accelerator (e.g.,a synchrocyclotron). Likewise, individual features of any two more ofthe foregoing implementations may be used in an appropriate combination.Elements may be left out of the processes, systems, apparatus, etc.,described herein without adversely affecting their operation. Variousseparate elements may be combined into one or more individual elementsto perform the functions described herein.

What is claimed is:
 1. One or more non-transitory machine-readablestorage media storing instructions that are executable to implement atreatment planning system for a particle therapy system, the treatmentplanning system comprising: a prediction model that characterizes theparticle therapy system and a patient to be treated by the particletherapy system, the prediction model characterizing the particle therapysystem at least in part by characterizing a timing at which the particletherapy system can deliver radiation; a relative biologicaleffectiveness (RBE) model that characterizes a relative biologicaleffectiveness of the radiation on tissue based on the timing of deliveryof the radiation; and a dose calculation engine to determine a doseregimen for delivery of the radiation to voxels of the patient, the dosecalculation engine being configured to determine the dose regimen basedon the prediction model and the RBE model.
 2. The one or morenon-transitory machine-readable storage media of claim 1, wherein thedose regimen specifies doses and dose rates at which the radiation is tobe delivered to the voxels; and wherein the treatment planning systemfurther comprises a sequencer to generate instructions for sequencingdelivery of doses in order to optimize effective doses determined by thedose calculation engine.
 3. The one or more non-transitorymachine-readable storage media of claim 1, wherein the prediction modelcharacterizes the particle therapy system based on a structure of pulsesof a particle beam produced by a particle accelerator.
 4. The one ormore non-transitory machine-readable storage media of claim 1, whereinthe prediction model characterizes the particle therapy system based ona maximum dose per pulse of a particle beam produced by a particleaccelerator.
 5. The one or more non-transitory machine-readable storagemedia of claim 1, wherein the prediction model characterizes theparticle therapy system based on a sweep time of a scanning magnet tomove a particle beam produced by a particle accelerator.
 6. The one ormore non-transitory machine-readable storage media of claim 1, whereinthe prediction model characterizes the particle therapy system based ona time it takes to change an energy of a particle beam produced by aparticle accelerator.
 7. The one or more non-transitory machine-readablestorage media of claim 1, wherein the prediction model characterizes theparticle therapy system based on a time it takes to move one or moreenergy-absorbing structures to change an energy of a particle beamproduced by a particle accelerator.
 8. The one or more non-transitorymachine-readable storage media of claim 1, wherein the prediction modelcharacterizes the particle therapy system based on a strategy forregulating doses of radiation.
 9. The one or more non-transitorymachine-readable storage media of claim 1, wherein the prediction modelcharacterizes the particle therapy system based on a time it takes tomove a collimator for collimating a particle beam produced by a particleaccelerator.
 10. The one or more non-transitory machine-readable storagemedia of claim 1, wherein the prediction model characterizes theparticle therapy system based on a time it takes to configure acollimator for collimating a particle beam produced by a particleaccelerator.
 11. The one or more non-transitory machine-readable storagemedia of claim 1, wherein the prediction model characterizes theparticle therapy system based on a time it takes to control a rangemodulator to change a Bragg peak of particles in a particle beamproduced by a particle accelerator.
 12. The one or more non-transitorymachine-readable storage media of claim 1, wherein the dose calculationengine is configured to determine times at which doses specified in thedose regimen are to be delivered to the voxels of the patient based onthe RBE model.
 13. The one or more non-transitory machine-readablestorage media of claim 1, wherein the dose calculation engine isconfigured to determine whether a voxel among the voxels containstargeted tissue, non-targeted tissue, or both targeted tissue andnon-targeted tissue, and to determine a dose rate of radiation to thevoxel based at least in part on whether the voxel contains targetedtissue, non-targeted tissue, or both targeted tissue and non-targetedtissue.
 14. The one or more non-transitory machine-readable storagemedia of claim 13, wherein the targeted tissue comprises diseased tissueand the non-targeted tissue comprises heal thy tissue.
 15. The one ormore non-transitory machine-readable storage media of claim 13, wherein,in a case that the voxel contains non-targeted tissue only, determiningthe dose rate of radiation to the voxel comprises determining to deliverno dose to the voxel.
 16. The one or more non-transitorymachine-readable storage media of claim 13, wherein, in a case that thevoxel contains targeted tissue or both targeted tissue and non-targetedtissue, determining the dose rate of radiation to the voxel includesdetermining to deliver ultra-high dose rate radiation to the voxel. 17.The one or more non-transitory machine-readable storage media of claim16, wherein the ultra-high dose rate radiation comprises a dose ofradiation that exceeds one (1) Gray-per-second for a duration of lessthan five (5) seconds.
 18. The one or more non-transitorymachine-readable storage media of claim 16, wherein the ultra-high doserate radiation comprises a dose of radiation that exceeds one (1)Gray-per-second for a duration of less than 500 ms.
 19. The one or morenon-transitory machine-readable storage media of claim 16, wherein theultra-high dose rate radiation comprises a dose of radiation that isbetween 40 Gray-per-second and 120 Gray-per-second for a duration ofless than 500 ms.
 20. The one or more non-transitory machine-readablestorage media of claim 1, wherein the dose regimen specifies doses anddose rates at which the radiation is to be delivered to the voxels; andwherein the doses are equivalent doses determined based on a weightingfactor from the RBE model.
 21. The one or more non-transitorymachine-readable storage media of claim 20, wherein the weighting factorcauses the dose to increase for a duration.
 22. The one or morenon-transitory machine-readable storage media of claim 2, wherein thesequencer is configured to sequence delivery of the doses based on oneor more of the following: a structure of pulses of a particle beamproduced by a particle accelerator, a maximum dose per pulse of theparticle beam, a sweep time of a scanning magnet to move the particlebeam, a time it takes to change an energy of the particle beam, a timeit takes to move one or more energy-absorbing structures to change theenergy of the particle beam, a strategy for regulating the doses, a timeit takes to move a collimator for collimating the particle beam, a timeit takes to configure the collimator, or a time it takes to control arange modulator to change a Bragg peak of particles in the particlebeam.
 23. The one or more non-transitory machine-readable storage mediaof claim 2, wherein, for a voxel among the voxels, the sequencer isconfigured to sequence delivery of a set of the doses in columns thatpass at least part-way through the voxel, each dose in the set beingdelivered at an ultra-high dose rate.
 24. One or more non-transitorymachine-readable storage media storing instructions that are executableto implement a treatment planning system for a particle therapy system,the treatment planning system comprising: a prediction model thatcharacterizes the particle therapy system and a patient to be treated bythe particle therapy system; and a dose calculation engine to determinea dose regimen for delivery of radiation to voxels of a patient, thedose calculation engine being configured to determine the dose regimenbased on the prediction model.
 25. The one or more non-transitorymachine-readable storage media of claim 24, wherein the dose regimenspecifies doses and dose rates at which the radiation is to be deliveredto the voxels; and wherein the treatment planning system furthercomprises a sequencer to generate instructions for sequencing deliveryof doses at rates determined by the dose calculation engine.
 26. The oneor more non-transitory machine-readable storage media of claim 24,wherein the prediction model is configured to characterize the particletherapy system based on one or more of the following: a structure ofpulses of a particle beam produced by a particle accelerator, a maximumdose per pulse of the particle beam, a sweep time of a scanning magnetto move the particle beam, a time it takes to change an energy of theparticle beam, a time it takes to move one or more energy-absorbingstructures to change the energy of the particle beam, a strategy forregulating the doses, a time it takes to move a collimator forcollimating the particle beam, a time it takes to configure thecollimator, or a time it takes to control a range modulator to change aBragg peak of particles in the particle beam.
 27. The one or morenon-transitory machine-readable storage media of claim 24, wherein thedelivery of radiation to the voxels of the patient is at an ultra-highdose rate, the ultra-high dose rate comprising a dose of radiation thatexceeds one (1) Gray-per-second for a duration of less than five (5)seconds.
 28. The one or more non-transitory machine-readable storagemedia of claim 24, wherein the delivery of radiation to the voxels ofthe patient is at an ultra-high dose rate, the ultra-high dose ratecomprising a dose of radiation that exceeds one (1) Gray-per-second fora duration of less than 500 ms.
 29. The one or more non-transitorymachine-readable storage media of claim 24, wherein the delivery ofradiation to voxels of the patient is at an ultra-high dose rate, theultra-high dose rate comprising a dose of radiation that is between 40Gray-per-second and 120 Gray-per-second for a duration of less than 500ms.
 30. The one or more non-transitory machine-readable storage media ofclaim 25, wherein, for a voxel of the voxels, the sequencer isconfigured to sequence delivery of a set of the doses in columns thatpass at least part-way through the voxel, each dose in the set beingdelivered at an ultra-high dose rate.
 31. The one or more non-transitorymachine-readable storage media of claim 25, wherein the sequencer isconfigured to sequence delivery of the doses based on one or more of thefollowing: a structure of pulses of a particle beam produced by aparticle accelerator, a maximum dose per pulse of the particle beam, asweep time of a scanning magnet to move the particle beam, a time ittakes to change an energy of the particle beam, a time it takes to moveone or more energy-absorbing structures to change the energy of theparticle beam, a strategy for regulating the doses, a time it takes tomove a collimator for collimating the particle beam, a time it takes toconfigure the collimator, or a time it takes to control a rangemodulator to change a Bragg peak of particles in the particle beam.